What's Wrong with Independent Birth of Organisms?

A review of Periannan Senapathy's book

And an investigation into the origin of life

      A review by Gert Korthof.   updated 16 May 2024 (first published 29 Dec 2002)

Introduction The origin of life is an age-old and unsolved problem. Independent researcher Periannan Senapathy came up with an extraordinary solution: the independent origin of all organisms, including humans (386, 387). It is an overambitious theory that seeks to replace everything Charles Darwin and evolutionary biologists have put forward the last 150 years. Although many of his objections to Darwin's theory are the same as those of creationists, his theory of random origin of genomes is the very opposite of design.    Senapathy did computer simulations and found that it was very difficult to find genes of bacteria in computer generated random DNA, but that it was easy to find the sequence of genes interrupted with meaningless pieces of DNA (introns). He concluded that random DNA sequences would automatically contain split genes typically of higher organisms. Next, he concluded that in a pre-biotic environment genes of plants and animals could be produced. The cumbersome and time-consuming Darwinian processes of mutation and natural selection would be completely unnecessary. It also implies that all other origin of life scenarios (including the RNA-world and pre-RNA-world) are superfluous.    Senapathy presents his extraordinary solution to one of the biggest problems in biology in an overconfident way. He is unaware of quite a few biological facts which happen to cause insurmountable problems for his theory. However, it would neither be fair nor interesting to disprove his theory using current biological knowledge (his book was published in 1994) or dogmatically use the theory of evolution to refute his views. It is relatively easy to find millions of objections to his theory, but to determine the most fundamental, the most profound objection –that is the objection that makes everything else superfluous– is far from trivial. I called it 'The elephant in the room'. It is a conceptual error, and is not depended on the latest research findings.    The results of this review go far beyond Senapathy's Independent Origin theory. This review evolved into a general Origin Of Life investigation with an emphasis on DNA. The comparison of different theories of evolution and origins of life continues to be a fascinating project. My motivation is: the effort deepens our insight into the Origin and Evolution of Life and enables us also to detect errors in other theories of the Origin of Life (312). In the end I will conclude that all the reasons why Independent Origin fails are indirect arguments for evolution.

Periannan Senapathy (1994) "Independent Birth of Organisms. A New Theory That Distinct Organisms Arose Independently From The Primordial Pond Showing That Evolutionary Theories Are Fundamentally Incorrect". Still available in amazon. Periannan Senapathy: thinking outside the box

Contents of this review A seductive computer experiment A test for randomness * Searching for exons, discarding introns Eukaryotes with intronless genes, prokaryotes with introns A static versus a dynamic genome A DNA sequence is not a genome * Genome-centered and information-centered approach * Everything you always wanted to know about sex Can a male or female arise from haploid cells? Can a male or female arise from diploid cells? Did prokaryotes arise from eukaryotes? All mammals require a mother Common descent versus independent origin The role of randomness The role of natural selection The role of mutation The role of adaptation: random perfection?     Ecology and the Food chain The role of time: the chronological order of life The role of place: the biogeography of life The clumpiness of morphospace The primordial pond is a free lunch Incompatible requirements for a primordial pond The final refutation of independent origin Origin of life What is life? Rerun the tape of life PLOS ONE article Nature Precedings articles Conclusion What I learned ( updated 3 Sep 2022 ) Conclusion after 20 years * ( added 14 Jul 2023 ) Appendix: Genetics Primer Notes Further Reading   *) These are the most important paragraphs

in a nutshell: Elephant in the room: Related page: Independent origin and the facts of life (a general overview)

Senapathy and the Greek Philosophers In Antiquity basically two solutions for the origin of organisms were developed: design and accident. The creationists Socrates and Plato argued for design. The Atomists Empedocles and Epicurus argued for accident. The atomists needed an infinite universe to explain why accident could produce highly improbable adaptations such as the eye. Darwin improved the 'accident theory' by eliminating the huge improbabilities and replacing them by natural selection. Senapathy's solution is non-creationist and non-Darwinist. But he does not invoke an infinite universe (96), so he bears the full burden of the Boeing-747 argument, and at the same time he dismisses the greatest improvement since Antiquity of the atomist naturalistic theory: full common descent, full gradual evolution, and full natural selection. Therefore, he has all the disadvantages of the 'accident theory' and must do without all the advantages of Darwinian evolution. Despite DNA, Senapathy ('immutable DNA') is closer to Greek philosophers than he knows: Lucretius believed in the fixity of species, and that all mutations occurred in one burst at the beginning of the world; all species were fully formed by spontaneous generation and did never change (85,p.149). Anaximander believed that all life arose in water (85,p.153). As an afterthougth Senapathy adds 'natural selection' (Fig.7). The Greek philosophers proposed at least two rounds of selection: one for viability, and one for fine adaptations by competition between individual animals. See: my review of David Sedley (2007) 'Creationism and its critics in Antiquity'.

A seductive computer experiment

"As I was working with the origin of genes from random genetic sequences, I realized that simple-to-complex gene evolution was quite unnecessary to explain the origin of complex genes found in multicellular creatures. I could demonstrate that the complex genes of multicellular creatures simply existed in very long random genetic sequences" (99)

"the genome would be mostly random DNA sequence with only small 'islands' of genes scattered in an ocean of meaningless DNA. Such an architecture actually exists in the genomes of all living multicellular organisms, with the intergenic sequences termed 'junk DNA'." (caption Figure 8.11)

1. split genes (genes with introns) are easy to find in computer generated random DNA sequences. Genes without introns are impossible to find.
2. so when in real life DNA sequences are randomly assembled from their building blocks, genes with introns will easily be formed by accident (split genes are primordial; they were never in one piece (200), and introns were never inserted)
3. since split genes are only found in eukaryotes (plants and animals), eukaryotes must have originated first
4. prokaryotes (which don't have introns) must have evolved from eukaryotes by losing introns (23).

sequence length possible sequences 1 4 2 16 3 64 4 256 5 1024 6 4096 7 16,384 8 65,536 9 262,144 10 1,048,576 50 1.27x1030 100 1.6x1060 200 2.57x10120 data from de Duve (270) codon=triplet; bases=4 Probability of the human genome Indeed, given enough time and resources, a computer could generate all the genomes in the world. Therefore, the probability is not zero. However, you do not have achieved anything if you do not calculate the probability of at least one complete genome (90). The probability of one gene does not help. The human genome happens to be very large. The haploid human genome has a length of ∼ 3 billion base pairs and the diploid genome is ∼ 6 billion base pairs (296). The number of possible sequences of 6 billion bases is not calculated by Senapathy. So he has no idea how many trials he needs to produce a human being. Yes, it is true: the larger a piece of DNA, the higher the probability of finding genes. But at the same time, the larger a piece of DNA, the harder it is to synthesize it abiotically. Please note, that the diploid genome cannot be reduced to the haploid because of heterozygosity (different alleles) and the X/Y pair. For illustration, we can calculate the possible sequences up to 200 bases length (see table). Surprisingly, there are more than 1 million possible sequences of only 10 bases (which is very much smaller than the smallest exon). A sequence of 200 bases is still nothing compared to 6 billion bases. The probability of the human sequence of 6 billion bases must be indistinguishable from infinite. We need to answer some basic but very difficult questions: How many sequences of 6 billion bases are possible? (random sequences) How many of those will produce a human being? (human sequences) How many sequences of arbitrary length will produce a human being? (not considered here) What is the smallest DNA sequence that produces a human? (not considered here) Let us assume for the moment that only one sequence of 6 billion bases produces a healthy human being, then the probability is 1/A. Since A is ∞ infinitely large, the probability is 1/∞ or ∼ 0 (zero). However, there are now 7 billion people on earth and since each individual has a unique genome, there are 7 billion unique sequences (B) that produce a human being. But that is not all. If we count all humans beings ever lived on earth, we arrive at an estimated number of 108 billion (266). So, the probability to hit a human genome is 108 billion divided by A, which is still close to ∞ (I guess). There is still more variability in the human genome we didn't include. For example, there are 38 million (mostly neutral) Single Nucleotide Polymorphisms (SNPs), 1.4 million bi-allelic indels and 14,000 large deletions in the human genome (295). There have been found 1,146,401 autosomal protein-coding SNVs in 15,336 protein-coding genes of 6,515 individuals (304). There are 117,277 mutations in The Human Gene Mutation Database. Furthermore, there are naturally occurring structural genomic variants in the human genome. Further, a survey showed that the average healthy person has about 20 genes knocked out (334). If we add every possible combination of SNP, mutation, indels and structural variants, B. rises above 108 billion (by an unknown amount). In Nov 2014 a new genome sequencing technology detected 22,000 segments of 50 to 5,000 bases in length that have never been reported before (347). More variation means more possible genomes able to create a human. Another way of estimating the amount of neutral variation –compatible with health– is the following. Evolutionary analyses indicate that natural selection has conserved five times more base pairs that don't code for proteins than ones that do (1.5%) (267), so we arrive at 7.5%. Another estimate is that up to 74% of the human DNA may be transcribed into RNA (232). Others estimate that probably around 60% of the mammalian genome is transcribed (261). Comparative analysis of 29 mammalian genomes reveals a high-resolution map of >3.5 million constrained elements that encompass ∼4% of the human genome and suggest potential functional classes for ∼60% of the constrained bases (268). Human chromosomes under a scanning electron microscope. ©Nature2017 Above we defined B. as all the sequences that produce a human being. However, in fact we should have added: how many sequences of 6 billion bases partitioned into 46 paired pieces (called 'chromosomes', see picture above) of specified length and contents. This is a far stronger requirement than simply 6 billion bases. Of course, any partition of the total DNA into chromosomes could produce a human, but the independent origin scenario demands the origin of the human genome as it is now. And then we have ignored we need not one human genome, but a female and a male genome! (See: §sex). Another serious restriction applies: the actual human genome (46 chromosomes) must conform a pattern of sequence and chromosome similarities with all of the 1.9 million species on earth, particularly, but not exclusively, primates and mammals. This significantly reduces the number of acceptable human genome sequences, because not any human genome fits that pattern.

• If we imagine the simplest conceivable organism whose hereditary mechanism depends on the processes of nucleic acid replication and protein synthesis, it would have to possess enough DNA to specify all the varieties of tRNA, the protein and RNA components of the ribosomes, the activating enzymes associated with the 20 amino acids, the various enzymes which replicate the DNA and make an RNA transcript of it, and more besides." (93)

• "It is impossible that an organism of this degree of complexity should arise by physico-chemical processes, without natural selection." (John Maynard Smith, 93, p.111)

• "The genes found today cannot have arisen randomly, as it were by the throw of a dice. There must exist a process of optimization that works towards functional efficiency. Even if there are several routes to optimal efficiency, mere trial and error cannot be one of them". (192)

A test for randomness

random DNA ©wikibooks.

1. A test for randomness (improved 1 Mar 2018)
   
   If DNA has directly arisen from random assembly of the building blocks and genomes are immutable, then all genomes we examine today should show randomness. A prediction is that the distribution of stop codons should be random. Is it? Actually there are two questions: What do we observe? What do we expect? Senapathy does not state this clearly at the beginning. Senapathy produces plots to answer both questions, but they are difficult to read, not well explained and do not seem to support his theory. A stopcodon is the DNA code for the end of the protein. If the distribution of stop codons in extant genomes would match a purely random distribution, it would be strongly suggestive for the random origin of genomes. The frequency of stop codons in a random computer generated DNA string must be calculated on the basis of the fact that 3 out of the 64 codons are stop codons (assuming this holds for the origin of life also). So we must expect that the average length of genes between two stop codons would be 64/3 = 21 codons (= 63 bases) (my calculation, Senapathy does not show this!). However, this is far too small for a real gene! The average length of a human gene is approximately 450 codons (1350 bases) (343). The Random Hypothesis fails spectacularly! End of story!
   According to Senapathy the expected length of genes in computer generated random sequences would vary from 0 (two stop codons next to each other) up to 500 or 600 bases, but "More than 95% of all random genes are shorter than 100 bases" (p.234). Indeed! This is the reason that ORF detecting software defines ORF's as a minimum of 100 codons (343).
   According to Senapathy genes in organisms are often 9000 bases (=3000 amino acids) long (p. 234). So this is far above the length of the genes found in the computer generated sequences. Therefore, one must conclude that typical eukaryotic genes could not be formed directly from randomly assembled DNA.
   

   
     Figure 7.4. See also the figure in PLOS ONE article were he repeats the idea.
   
   

   Nevertheless, Senapathy is not discouraged by this result. He invokes 'a kind of processing' at the RNA level (see figure 7.4) that results in eliminating all the RNA sequences with too many stop codons (corresponding to introns) and combining long ORFs (corresponding to exons). So, he thinks the test for randomness is a success because he invoked 'processing' and because he thinks that is a permitted step in a Origin-of-Life scenario. But this 'processing' is nothing else but RNA splicing because it happens at the RNA level. The DNA stays intact, it does not change at all. Therefore, the DNA of extant eukaryotes must still have the signature of random DNA with abundant stop codons. But it does not. This kills the whole idea.
   
   Further, RNA splicing occurs after transcription– a process he simply assumes. And splicing occurs in the nucleus– a cell component he simply assumes. Where does his nucleus come from?
   
   A further problem with this idea is that he assumes that the key sequences necessary for proper splicing (splice recognition sites) are just there. How convenient! But, splice recognition sites are by defintion non-random. So, it doens't help very much that introns are random sequences. Splice recognition sites are non-random and they are enough to kill his theory (419).
   Furthermore, the processing assumes full-blown splicing machinery. This is cheating. One must not only find exons! This is not shown in the computer simulation (Figure 7.1)! So we should not search for: TO BE OR NOT TO BE, but:
   
   wxyzTOabcdefghi ... wxyzBEabcdefghi ... wxyzORabcdefghi ... wxyzNOTabcdefghi ... wxyzTOabcdefghi ... wxyzBEabcdefghi
   ( wxyz and wxyz represent splice recognition sites (363) and ... represents an intron). How else can the words (exons) TO BE OR NOT BE be recognized? (26). The real number of bases essential for proper splicing is unlikely to be less than 10 and is plausibly as high as 30 (39). There is a 5' splice site, 3' splice site and a branch site in the middle of the intron (Intron splicing). To be correctly processed to proteins, begin and end of exons need to be recognised. However, this would make the task of finding them in a random sequence far more difficult than Senapathy imagined.
   
   

2. Structure of an eukaryotic gene, in: Senapathy, Appendix: Genetics Primer, figure 10, p. 555.

   
   Start codons: 25 Sep 2011, 25 Feb 2018 Although, he knows start codons (see figure), Senapathy mistakenly ignores them in his calculations. However, an Open Reading Frame (ORF) is defined as the sequence between a Start codon and a Stop codon. The necessity of Start codons (usually AUG) gives a further restriction of the length of ORFs. Start codons occur 1 in 64 codons (see genetic code table). If we combine Start and Stop codon frequencies, the predicted average ORF length would be reduced from 21 to 17 codons! (362) There is absolutely no room for introns and exons in such a short piece. So, the discussion of introns and exons is totally irrelevant. See further: The elephant in the room.
   
   
3. Transposable Elements 9 Nov 2012
   Transposable Elements (transposons) constitute two-thirds of our own genome and 85% of the corn genome (297). They originate by duplication. Senapathy extensively discusses transposons in Chapter 4. He knows the work of Barbara McClintock. As far as I can see he does not make an estimate of what percentage of a genome consists of transposons (in humans 45%). The fact that transposons move means that the genome is dynamic. This contradicts his 'immutable' genome. Senapathy is not worried by such a contradiction.
   
   
4. Long terminal repeats 9 Nov 2012
   Long terminal repeats (LTRs) are sequences of DNA that repeat hundreds or thousands of times. They are found in retroviral DNA and in retrotransposons. Because of the repeats they are not random DNA.
   
   
5. Codon usage bias
   The genetic code is redundant. The number of codons for 1 amino acid varies from 1 - 6. For those having more than one codon, the different codons are used in unequal frequency. Some are rarely used, others with high frequency. For the amino acid LEU the most frequently used codon is used 140 times more often than the least frequently used codon (33). This is a genome wide bias. Some species such as Thermus thermophilus avoid certain codons almost entirely (306). However, there should be no such huge codon bias when genomes arose by chance from the primordial pond. In the independent birth scenario all codons for an amino acid are expected to occur on average with the same frequency. There is an explanation for codon usage bias: (354).
   
   
6. Non-random stop codons 4 Jan 2013
   In the standard genetic code, there are 3 stop codons:  TAA ,  TAG ,  TGA . In a random genome the stop codons are expected to have equal frequency (about 33%). However, the distribution of stop codons within the genome of an organism is non-random. For example, the E. coli K-12 genome contains 63% TAA, 29% TGA, and 8% TAG (wiki), so is highly non-random. Furthermore, the stopcodons are clustered in the genetic code table: they all start with T and two start with TA. That is not a random distribution.
   Finally, or better: firstly, the whole idea of a 'stop codon' depends on a full standard genetic code! And in order to function as a stop codon a Release factor is required, which is a protein. Where does that protein come from? See: elephant in the room.
   
   
7. Mononucleotide repeats 18 Nov 11
   Are nucleotide sequences actually used by organisms a random sample of all the possible sequences encoding that particular amino acid sequence, or do they deviate from a random choice? Short mononucleotide repeats occur at about the frequency expected by chance, but longer mononucleotide repeats are substantially rarer than predicted by the null model in all three organisms C. elegans, S. cerevisiae, and E. coli. For example, in E. coli, the codon TTT is avoided in favor of TTC at positions immediately followed by a T. This reduces the frequency of runs of four Thymines, and thus indirectly also of longer stretches of Thymine that necessarily contain runs of four. (237). Explanation: as mononucleotide repeats are prone to slippage during transcription and translation, the most parsimonious explanation is selection against error-prone nucleotide composition.
   
   
8. Dinucleotide frequency 12 Nov 12 update
   

   AA AT AC AG TA TT TC TG CA CT CC CG GA GT GC GG

   Since the genome of any organism arose randomly, each genome must have identical statistical properties. How could they differ significantly? For example, within the human genome each of the 4x4=16 possible dinucleotides (see table) should be present in equal frequency (100/16=6.25%). However, there is a notable depressed level of the CG dinucleotide (0.99% compared with 9.80% of TT dinucleotde) (108, p. 11). Vertebrates: CpG dinucleotides have long been observed to occur with a much lower frequency in the sequence of vertebrate genomes than would be expected due to random chance. On the other hand, there are CpG islands: genomic regions of several hundred base pairs with a high GC content. See also: Chargaff's GC rule. In contrast, the genome of most invertebrates contains largely unbiased frequencies of CpG dinucleotides (383) These facts alone refute random origin of DNA sequences.
   
   
9. Microsatellites, or short tandem repeats 28 sep 12
   Microsatellites consisting of two, three or four nucleotides repeats and can be repeated 3 to 100 times. Especially, the higher repeats very unlikely occur in random DNA. They are non-random.
   
   
10. Chargaff's cluster rule
    Apart from the first parity rule (A=T C=G), Erwin Chargaff made three other fundamental observations on the base composition of DNA, which are only now being incorporated into mainstream biology. The first species-invariant observation was that individual bases are clustered to a greater extent than expected on a random basis (197) which contradicts random origin.

    "Another consequence of our studies on deoxyribonucleic acids of animal and plant origin is the conclusion that at least 60% of the pyrimidines occur as oligonucleotide tracts [runs] containing three or more pyrimidines in a row; and a corresponding statement must, owing to the equality relationship [between the two strands], apply also to the purines." (197)

11. Chargaff's second parity rule
    The second species-invariant observation was that Chargaff's first parity rule also applies, to a close approximation, to single-stranded DNA. The validity of the rule became clearer when full genome sequences became available. For example, the "top" strand of Vaccinia virus has 63921 A, 63776 T, 32010 C, 32030 G (197). The bacterium Sarcina lutea has an extreme (A+T)/(G+C) ratio of 0.35 (Biopolymer Chemistry). If DNA were random 25% A, 25% T, 25% C, 25% G are predicted. So, again random origin is refuted.
    
    
12. Chargaff's GC rule
    The ratio of C + G to the total bases (A+C+G+T) (GC-content) tends to be constant in a particular species, but varies between species (197). The CG-content or AT/CG ratio of genomes is not 1:1. Already in 1952 CG percentages as low as 34,8% have been discovered in the DNA of insect viruses (34). In the bacterial kingdom the CG percentage varies from 25% to 75% (35). Acidianus infernus and Methanococcus jannaschii have 31% GC-content (255). A species with an extremely low GC-content is Plasmodium falciparum: ~20% (wiki). The genomes of extremophile organisms such as Thermus thermophilus are particularly GC-rich (wiki). Although some deviation from the mean of 50% is to be expected in a random sequence of DNA, extreme deviations are highly improbable and contradict random origin.
    
    
13. A test for randomness of phase 0,1,2 introns 16 Mar 11
    An intron could start between or within triplet codons. The same is true for the end of an intron. Between codons is called (phase 0), within codons is called phase 1 (after the first base) or phase 2 (after the second base). If introns have the same phase at the beginning and end, they are symmetric, otherwise they are asymmetric. There are three symmetric intron types (0,0), (1,1), and (2,2) and six asymmetric types (0,1), (0,2), (1,2), (1,0), (2,0), and (2,1). The theory of random origin of introns and exons predicts that all 9 intron phases should have approximately the same frequency in random DNA. Already in 1992 Fedorov et al. showed that the proportions of the three intron phases were significantly unequal. In 1993 Green et al. showed excess phase 0 introns and excess symmetric exons in ancient conserved regions (ACRs). Later publications based on GenBank give the same results. The proportions of three intron phases and frequencies of nine associations of introns showed significant nonrandom distribution: 48% phase 0, 28% phase 1, and 24% phase 2 and all symmetric exons (0,0), (1,1), and (2,2) showed significant excess over a random prediction (199). Conclusion: random origin is refuted.
    
    
14. A test for randomness of proteins
    Ptitsyn (136) concludes "that primary structures of proteins are basically just the examples of random amino acid sequences which have only been 'edited' during biological evolution". Pande et al (137) examine the possible random nature of protein sequences. The hypothesis was that proteins are slightly edited random sequences. They found pronounced deviations from pure randomness. Keefe & Szostak (138) state that "Functional primordial proteins presumably originated from random sequences". However, even if proteins emerge spontaneously prebiologically, this is irrelevant for the origin of life, because proteins cannot be translated in to DNA (Crick's central dogma of molecular biology). So, the result is useless for the question of random origin of DNA. Douglas L. Theobald (130) wrote "Many proteins probably do exist that have independent origins. For instance, in the Metazoa certain protein domains have probably evolved de novo that are not found in either Bacteria or Archaea. However, the independent evolution of unique Metazoan proteins, by itself, is not evidence for or against UCA." (UCA= Universal common ancester).
    
    
15. Non-random genome architecture
    Are genomes randomly arranged assemblages of genes or is gene order non-random? Genome architecture (that is, the order, spacing and orientation of genes in the genome) can be highly non-random (239).
    
    
16. Low-Complexity Sequences or Repetitive Sequences
    Eukaryotic genomes contain vast amounts of repetitive DNA derived from transposable elements (TEs) (269). The more Low-Complexity or Repetitive Sequences occur in eukaryote genomes, the more difficult they are to explain under the random origin scenario. The most difficult to explain are tandem repeats.
    
    
17. Paul Davies about genomes
    
    

    "If genomes are information-rich, then they have to be random (or almost so). If biological organization is random, its genesis should be easy. [!] The vast majority of possible sequences in a nucleic-acid molecule are random sequences. Only a tiny, tiny fraction of all possible random sequences would be even remotely biologically functional. A functioning genome is a random sequence, but it is not just any random sequence. It belongs to a very, very special subset of random sequences" (40)

    So Senapathy is right about genomes being mathematical random, but its production is not easy because only a tiny, tiny fraction of the genomes are functional. Without knowing it, Davies refuted Senapathy.

Searching for exons, discarding introns and enhancers

Figure from: 195.

The changing paradigm of intron retention: regulation, ramifications and recipes (414)

Noncoding DNA: junk DNA?

Eukaryotes with intronless genes, prokaryotes with introns

A static versus a dynamic genome

"In 1947 Barbara McClintock discovered, through a series of genetic studies in the corn plant (maize), that some genes were jumping around the genome." page 107 (chapter 4)
"Conclusion: Transposons cause genetic effects which are incapable of any evolutionary potential; these are passive parasitic processes occurring in immutable genomes" page 117 (chapter 4)

Human genome partitioned in different fractions.
Transposons are the dynamic element in the human genome.

Age distribution of Transposable Elements in the human genome,
The graph shows the fraction of the current genome that consists of TEs that inserted at a given time in the past.
Futuyma, Kirkpatrick, (400).

A DNA sequence is not a genome

"We shall see how the random combinations of genes in a primordial pond could lead to the assembly of numerous genomes." (p.9).

(1) DNA and chromosomes without the biological context

1. Why a double helix? DNA is a double helix: that is redundant. The information is only in 1 string. Which one?
2. Why right-handed DNA? The DNA of every organism on Earth is a right-handed double helix. But, essentially all known chemical reactions produce even mixtures of right-handed and left-handed molecules. In principle, a DNA or RNA strand made from left-handed nucleotides should work just as well as one made of right-handed bricks (396). If the genomes of organisms arose directly from a primordial pond, and are immutable, then we should expect a random mix of organisms with left-handed and right-handed DNA. Furthermore, the distribution of the left-handed and right-handed organisms should be randomly distributed in the Linnean hierarchy, that is in families, genera and species.
3. Why only 4 bases forming two pairs, while more than 100 nitrogenous bases are possible? (160). He cannot just assume it because he starts with DNA.
   • Why not 6 bases forming 3 pairs with a total of 6x6x6=216 different triplets? (403, 404).
   • Why not use 20 different bases to code for 20 amino acids? (111).
   • Why are there 2 types of bases: purine and pyrimidine bases?
   The problem of prebiotic synthesis of the DNA bases is the same for independent origin and evolution, except that life did not start with DNA (but with RNA or something even more simple). However, the fact that the 4 bases in DNA are common to all life is only a problem for independent origin.
4. Why do the sugars in DNA have five- (pentose) rather than six-membered (hexose) rings? (430).
5. Why does the DNA backbone universally consist of deoxyribose and phosphate? Why does RNA use ribose instead of deoxyribose and Uracil instead of Thymine? The sugar deoxyribose is harder to make, and in present-day cells it is produced from ribose in a reaction catalyzed by a protein enzyme, suggesting that ribose predates deoxyribose in cells (260). Alternatives for DNA are chemically possible (256). Senapathy a priori excludes any evolution from simpler bases and sugars to the current ones.

The Codon Table, page 548 Appendix Genetics Primer. SENAPATHY.

1. Codon length: Why a codonlength of 3 bases (triplet) resulting in 4x4x4=64 combinations? A codonlength of 4 increases the number of possible codons to 4x4x4x4 = 256 (404). A code with only two bases and a codon length of 4 (quadruplet codons) is also possible (111). A codon length of 6 (Sextuplets) is possible.
2. Why a commaless triplet code? (126)
3. Why a non-overlapping code? Each nucleotide is part of only one triplet (three nucleotides specify each amino acid in a protein) (126)
4. Reading Frame: assuming a triplet code and a linear sequence of bases, where to START reading? How to define the first base of a triplet? With a triplet code there are 6 possible reading frames: 3 in one direction and 3 in the other direction. Since there are 2 strands in DNA, there are in total 12 possible reading frames. Which one is the 'correct' one? Can both strands be used at different locations? etc.
5. Directionality: DNA is a linear sequence of letters. The genetic code has directionality or polarity. However, such sequences can be read in two directions. Triplets will code for different aminoacids and ORFs will produce two different proteins when read in opposite directions. Importantly, STOP codons will become aminoacids and some aminoacids will become STOP codons when read in opposite directions. Which is the correct direction?
6. Coding strand and noncoding strand: DNA is double-stranded, but only one strand serves as a template for transcription at any given time. This template strand is called the noncoding strand. The nontemplate strand is referred to as the coding strand because its sequence will be the same as that of the new RNA molecule. In most organisms, the strand of DNA that serves as the template for one gene may be the nontemplate strand for other genes within the same chromosome (!). How is decided which strand is used? Senapathy ignores this. (Nature Scitable, Coding strand).
7. Why a degenerate code? (redundant coding): why are there 61 meaningful triplet codons? 20 triplets would be enough, so 41 codons are redundant. What is the problem if 41 'codons' are unused? Is it necessary that all 61 codons are used? No, certainly not. Yes, we know now that all 61 codons are used, but the independent scenario must explain this fact.
8. Stop codons: Why choose 3 'stop' codons (but first see: elephant in the room!) UAA, AUG, UGA? Why not 1, 2 or 4 'stop'-codons? Genetic codes with only 2 stop codons do occur naturally in eukaryotes (335) and prokayotes (338), (204). In some ciliates, like Paramecium, only UGA is a stop codon. This changes stop-codon statistics from 3/64 to 2/64 or 1/64. Quite a difference! Senapathy does not give a justification for using 3 'stop-codons'. One cannot just assume that 3 are somehow 'natural'. Which chemical law?
   Another question: Why is there a strong bias for 'stop' codon usage (frequency) in different species? For example, in Escherichia coli W3110 the codon UAG has a frequency of 0.2 per thousand compared with CUG has 53.1 per thousand (source).
9. Start codon: Why only one and nearly universal Start codon (362) (AUG = MET = methionine)? A start codon is necessary because bases must be read in triplets and the correct base must be identified as the first of the triplet. The start codon must hold throughout the whole genome. Misidentifying the first base of a triplet would result –if translated at all– in a different amino acid and consequently in a different protein (Just as in case of a one-base deletion or insertion).
10. Amino acids: Life universally uses the same 20 amino acids. Why only 20 amino acids while 150 amino acids are possible in nature? (160). Why exactly those 20 amino acids and not others? (the universal use of the same 20 amino acids points strongly to common descent of all life). Only 12 of the 20 amino acids can be synthesized prebiotically, the other 8 can only be synthesized by living organisms (208). So independently arisen genomes coding for 20 amino acids cannot function because 8 amino acids are missing.
11. Nonrandom redundancy (degeneracy) of the code is not random (very imporant!). The codons for an amino acid are clustered. Why? This is the structure of the genetic code. A redundant code is a logical consequence of 64 triplet-codons coding 20 amino acids and 3 stop codons. So, on average an amino acid is coded by 3 codons, the real number varies from 1 - 6. Mostly, the codons for a particular amino acid have the same first two letters. The third letter varies most. This is not random! Furthermore:
12. Why does the genetic code minimize the chemical consequences of amino acid mistakes? Optimal code, Steve Freeland (234).
13. Neighboring triplets in the genetic code tend to specify biochemically similar amino acids, so that single-nucleotide substitutions rarely lead to radical amino acid replacements (238). This is a non-random code!
14. Why is there a codon usage bias? (see also: codon usage database). Some codons for the same amino acid are used very frequently, others rarely. Codon usage should be random in the independent origin scenario.
    Info: this is not about the structure of the genetic code, but about how often the codons are used in a genome. Statistically, one would expect that all codons occur in about the same frequency in DNA. This is not so. For example. there are differences in the frequency of occurrence of synonymous codons (139). For the amino acid LEU the most frequently used codon is used 140 times more often than the least frequently used codon (33). In the bacterial kingdom the C+G percentage varies from 25% to 75% (35).
15. Why is methionine the starting amino acid in the synthesis of most protein chains if DNA arose spontaneously? (Initiation Codons, eukaryotes)

• Chemical necessity?
  The only possible escape would be that the genetic code would be a chemical necessity. In that case the same genetic code would be produced automatically again and again. Is the code a chemical necessity? Is seems now likely that only 25% of the codons can be explained by a chemical affinity of amino acid and codon-RNA, and 75% of the codons are arbitrary assigned (127, p.174). The 25% follows from the universal laws of chemistry and thus will be the expected outcome on any planet. However, 75% of the genetic code must be explained by common descent. That is an inherited and 'frozen' accident. Independent origin cannot explain universal arbitrary features of the genetic code because there cannot be millions and trillions of trials with exactly the same outcome! Unless one particular 'frozen accident' is inherited by all descendant species. This is called evolution by common descent and modification. Of course the theory of evolution needs to explain how the genetic code originated, but the fact that every species has the same genetic code can only explained by common descent. The frozen accident theory may be not the most elegant theory, but at least it is not ruled out by probability theory! Any talk about 'common pool of genes' destroys a truly independent origin of life. Conclusion: the universal genetic code is the strongest argument against independent origin I can think of (128).
  
  
• Inheritance of the code
  Additionally, and crucially, whatever its origin, the genetic code is encoded in DNA itself by Transfer RNAs (tRNAs). The attachment of an amino acid to its codon is the result of the aminoacyl tRNA synthetase which adds the aminoacyl group to its allocated tRNA. This embodies the connection between DNA triplets and amino acids (82). The human genome encodes more than 500 tRNA genes. There are at least 20 aminoacyl tRNA synthetases. This is the problem: the DNA sequence of an organism could be random, its translation cannot be random. The translation machinery must be immutable. The translation machinery gives meaning to a meaningless sequence of bases. tRNA and aa-tRNA genes must be exactly identical for all organisms on earth. So, the biggest problem is not producing random DNA sequences, but producing highly specific and invariant tRNA and aa-tRNA and incorporating them in each organism. How does the Primordial Pond guarantee this? How does a completely random process guarantee that each and every individual organism has exact the same set of 64 tRNA and aminoacyl-tRNA-synthetase genes? Extremely unlikely.
  This looks like one of the many problems of Independent Origin. But it appears now that it is the most fundamental and deepest obstacle for an independent origin scenario: reading and interpreting a DNA sequence with the same translation code for every individual in the primordial pond.
  
  
• Origin of the code

  "The important point to realize is that in spite of the genetic code being almost universal, the mechanism necessary to embody it is far too complex to have arisen in one blow. It must have evolved from something much simpler. Indeed, the major problem in understanding the origin of life is trying to guess what the simpler system might have been". Francis Crick (1981) Life Itself, p.71 (184).

  Is gradual evolution of the genetic code compatible with independent origin? Independent origin of complete eukaryotic genomes must assume the full set of 20 amino acids, because the current genetic code codes for 20 amino acids. Less than 20 will prevent the production of functional proteins. It cannot start with a subset of amino acids and later add additional ones (as in evolutionary scenario's). Evolutionary scenario's make the problem easier. For example, Wong proposed the evolution of the genetic code in two phases. In the first phase 6 - 10 amino acids were assigned to 61 codons. The code then expanded by the addition of phase-2 amino acids (145a). Any gradual evolution of the genetic code is incompatible with Senapathy's scenario. Not only the genetic code but also the genome would have to evolve. Both are (and must be) fixed in Senapathy's scenario. So, the burden to explain the abrupt origin of a full-blown 64/20 genetic code rests on Senapathy's shoulders. He did not address this difficulty (see also § 27: PLOS One article). See for other proposals of the evolution of the genetic code: (158).
  
  

The Standard Genetic Code contains 18 fragile codons (red) that can be changed into a STOP codon by a single point-mutation and whose mistranscription can therefore generate nonsense errors. The remaining 43 sense codons are "robust" to such errors. Six amino acids are encoded exclusively by fragile codons ("fragile amino acids", shaded), ten amino acids are encoded exclusively by robust codons ("robust amino acids", unshaded) and four amino acids can be encoded either by robust or fragile codons ("facultative amino acids", hatched shading). We observe a 8% depletion of fragile codons in single-exon genes in the human genome that is highly significant. After Brian P. Cusack et al (240)

1. Why a DNA genome?
   Why are the first genomes made of DNA? What's wrong with RNA genes or RNA genomes? Double-stranded RNA viruses do exist. RNA genomes would be simpler because they could consist of rna genes which do not require a genetic code to be present, since no proteins have to be produced.
   
   
2. A sequence constructed with any 4 'letters' is not DNA
   A sequence constructed with 4 different 'letters' is not DNA because the letters must be able to chemically pair specifically and reliably. They must consist of pairs. For example: A must pair with T, C with G. So not any 4 letters will do. A restriction applies which cannot be ignored. Furthermore, they must not only be able to pair, they must be able to separate temporarily for DNA replication. This pairing is completely absent from all computer simulations. Strangely, it seems irrelevant for computer simulations. But it cannot be ignored if one wants to solve the origin of life because DNA cannot exist without pairing. "All organisms, from bacteria to humans, face the daunting task of replicating, packaging and segregating up to two metres (about 6 × 10⁹ base pairs) of DNA when each cell divides." (340). See: cell division (below).
   
   
3. A single-stranded linear sequence of 4 letters is not DNA
   A sequence constructed with 4 different letters is not DNA because Prokaryotic and Eukaryotic DNA have a double stranded helix. Single-stranded DNA (ssDNA) viruses exist. Double-stranded DNA (dsDNA) creates a problem. In nature usually only one strand of a particular region in DNA (sense strand, or positive sense, coding strand) is translated into proteins. The other non-sense or antisense strand ('non coding strand', 'complementary strand', 'antisense') is not translated. Senapathy's example in figure 1 is a virtual single-stranded DNA sequence and is supposed to be the coding strand. He ignores that both strand could be used as a code. How is it decided what is the coding and what the complementary strand?
   In most organisms, the strand of DNA that serves as the coding template for one gene may be noncoding for other genes within the same chromosome (341). Amazingly, there are several protein coding genes encoded in the opposing strand of another gene! (Overlapping genes). These are genes within genes. Example is the gene for neurofibromatosis type I (NF1) which contains 3 genes in the opposing strand of the intron (167). If genomes are random sequences, then Senapathy should predict that genes are located randomly on either strand. If there is an excess of genes on one strand, the hypothesis is falsified. The problem is that his approach is incapable to incorporate all these complications because he uses only single-stranded sequences.
   
   
4. A linear sequence of A,T,C,G is not a gene
   A sequence of the bases A,T,C,G of arbitrary length is not a gene (or exon) because the length must be a multiple of 3. The reason: the code is a triplet code. This objection is related to the genetic code (see above).
   
   
5. Double-stranded DNA does not form spontaneously 1 Feb 2012
   The spontaneous formation of double-stranded DNA has never been observed. Double-stranded DNA is always formed by semi-conservative replication on the basis of an pre-existing double-stranded DNA polymere (Meselson-Stahl, 1958). So, of each double-stranded DNA molecule one strand is inherited as it is from the mother DNA molecule and the other strand is newly synthesized.
   
   
6. DNA requires a 'DNA synthesizer'
   Even if we assume statistics allows for a complete eukaryotic genome in a random sequence of A,T,C,G, then still those DNA sequences must be synthesized from chemical building blocks: bases, deoxyribose, phosphate. It turns out that this is extremely difficult abiotically (83). Enzymes are required: Deoxyribose is generated from ribose 5-phosphate by ribonucleotide reductases. Nucleotides, the building blocks of DNA have never been produced in any prebiotic synthesis experiment (365). The enzyme dihydrofolate reductase is required for making nucleotides. At the same time enzyme inhibitors prevent DNA synthesis. This is fatal for de novo DNA synthesis. Finally, DNA polymerase III is well-known for its blazing catalytic speed of ~ 1000 base-pairs per second (360), so replicating DNA without any enzymes would take an eternity.
   (Mainstream science has the RNA-world and the Pre-RNA world), but this is unavailabe in Independent Birth of Organisms.) Even in the lab it is difficult to synthesize a small eukaryotic chromosome, let alone a complete genome (329), (330). However, recent experiments show that the building blocks of RNA and DNA could have been produced abiotically starting with Urea (405).
   
   
7. How to build a genome. Lessons from synthetic genomes: the first synthetic genome (a bacterial genome) was created from scratch in the lab by Craig Venter in May 2010.
   1. The first lesson: this work didn't create a truly synthetic life form, because the genome was put into an existing cell (129). (the original genome was carefully removed before it received the new genome).
   2. The second lesson: it is very difficult to create a 1-million-base genome. Blue Heron (The Gene Synthesis Company) has mastered the art of synthesizing relatively long, entirely accurate sequences, and stringing them together to create gene-sized fragments on the order of hundreds to thousands of bases. However, the human genome is 3000 times bigger! To assemble a one million genome from 1k pieces the process involved, according to Venter, "invention after invention after invention of new ways to do things" and "There were literally thousands of hurdles that had to be overcome" (201).
   3. The third lesson: errors! Initially the attempt failed because the artificial genome failed to take control of the cell. The cause was a single-base mistake which delayed the project 3 months (129).
   Only a handful of genomes have been synthesized so far, mostly for bacteria. Today (2020) it is still a huge challenge to create fragments of a few thousand bases, let alone to create all the 16 chromosomes of the yeast Saccharomyces cerevisiae (a eukaryote). The longest yeast chromosome under construction is around 1.5 megabases (mega=million). The complete genome is about 12 million base pairs. It does not matter whether these fragments are random or specified sequences, the fragments need to be assembled to produce whole chromosomes (380).
   
   
8. DNA synthesis costs energy
   "Each building block needs to be activated, or chemically charged, before it can be incorporated into a polymer. Activation requires a preexisting source of chemical energy." (256). "It has been known for nearly 20 years that chromatin assembly is an ATP-dependent process" (146). There are two energetic components: the costs of nucleotide synthesis and the polymerization cost needed to make a DNA or mRNA molecule (188). Finally, DNA synthesis costs more energy than RNA synthesis. DNA replication is energy consuming process. So without ATP DNA synthesis could never happen.
   
   
9. Even the smallest genome is too long   2 Aug 2012
   The genome of the urogenital bacterial parasite Mycoplasma genitalium is 582,970 base pairs long (525 genes), making it one of the smallest genomes of any independently dividing cell – for comparison, the gut bacterium Escherichia coli has 4.6 million base pairs and around 4,200 genes (282). Compare with the smallest eukaryotic genome of Encephalitozoon intestinalis: 2.25 million base pairs. Despite this 'small' genome size, the genome of Mycoplasma genitalium is too long to originate spontaneously (apart from all other requirements for a genome).
   
   
10. DNA has to be replicated every cell division 6 Jun 2023
    DNA has to be replicated every cell division. This has nothing to do with coding for proteins. DNA replication requires proteins. Those proteins require specific DNA sequences called: Origin of Replication. Those sequences are about 100 basepair long. There may be as many as 100,000 origins of replication in the human genome. Without OoR DNA can not be copied and a cell cannot divide (401).
    
    
11. Watson-Crick base pairing is by far insufficient for DNA copying fidelity: 8 Jul 2023
    Despite its beauty, Watson-Crick complementarity is absolutely insufficient to ensure an acceptable fidelity of replication, even with perfect raw materials. Fidelity of nucleotide attachment depends not on complementarity, but on active involvement of DNA polymerases. (410).
    
    
12. A genome is not a random collection of genes (1)   6 Aug 2012
    

    "Because genes present in the random DNA sequences in the primordial pond were randomly assembled into various genomes" (p.377). added 5 Jul 2023

    Even if all eukaryotic genes are produced abiotically, on statistical grounds it can be excluded that random assembly of those genes will produce a viable eukaryotic genome. Let alone an eukaryotic organism. The number of combinations of genes and their interactions that need to be probed (by natural selection!) is infinitely large, so it would take an infinite amount of time to test the whole thing. "It is not feasible to understand evolved organisms by exhaustively cataloging all interactions in a comprehensive, bottom-up manner". For only 10 genes there are already 115,975 possible interactions (283). And then we ignore when (development), where (tissue, organ), at what level genes are expressed and when they are shut down.
    Amazingly, Senapathy seems to be aware of the problem:

    "Out of a great number of combinations of different kinds of genes, only one genome can produce such a viable organism" (p.295) added 5 Jul 2023

    but then he ignores the whole problem and continues.
    
    
13. A genome is not a random collection of genes (2)
    "Animals are more than the sum of their genes – it is the regulated expression of genes across space and time that helps to differentiate egg from embryo, leg from wing or bat from fly.". (356)
     
14. A genome is not a random collection of chromosomes   29 Sep 2012
    Aneuploidy is a deviation from the standard number of chromosomes of a species: one or more chromosomes extra or missing. In humans, loss of any autosome (non sex chromosome) is lethal. Carcinogenesis has been shown to be initiated by random aneuploidy (292). Aneuploid embryos usually die.
    
    
15. RNA genes are ignored   24 Sep 2012
    Genes that code for proteins have start en stop codons and are translated into proteins following the Genetic Code table. However, by mid-2009 evidence for at least 6000 human RNA genes had been obtained. RNA genes are difficult to identify using computer programs: there are no open reading frames (ORFs) to screen for (274, p. 262). Senapathy's search for genes depends on Open Reading Frames (sequences without STOP codons). This method fails to find RNA genes. The ENCODE project found 18.441 RNA-genes (290). RNA genes that were known when Senapathy wrote his book are Transfer RNA (tRNA) (mentioned on page 556) and Ribosomal RNA (rRNA) genes (not mentioned).
    
    
16. A DNA sequence is not a chromosome
    Animals and plants cells do not contain naked DNA. For example, the diploid human genome contains 6 billion base pairs of DNA per cell with a total length of 2 meter packaged into 23 pair of chromosomes. Because each base pair is around 0.34 nanometers long (one-billionth of a meter), each diploid cell therefore contains about 2 meters of DNA. This creates the DNA Packaging Problem: (supercoiled DNA) How is all of that DNA packaged into chromosomes and into the nucleus? (320) and how is it unpackaged and unwinded in order to read genes.
    
    

    A DNA sequence is not a chromosome     Human chromosomes under a scanning electron microscope. ©Nature2017 "A DNA sequence isn't enough; to understand the workings of the genome, we must study chromosome structure. Far from being the random result of packing 2 metres of DNA into a sphere perhaps 10 micrometres across, the structures vary across cell types and exert an as-yet-mysterious influence on gene expression." (176). "We usually think of genomes abstractly as one-dimensional entities that are purely defined by their linear DNA sequences. Reality, of course, is far more complex. The DNA helix is folded hierarchically into several layers of higher-order structures that eventually form a chromosome" (177). "Comparing the length of metaphase chromosomes to that of naked DNA, the packing ratio of DNA in metaphase chromosomes is approximately 10,000:1 (depending on the chromosome). This can be thought of as akin to taking a rope as long as a football field and compacting it down to less than half an inch. This level of compaction is achieved by repeatedly folding chromatin fibers into a hierarchy of multiple loops and coils." (320).

    
    

    G-banded human kayrotype, male, 46XY     G-banded human kayrotype, male, 46XY. © www.pathology.washington.edu

    
    A DNA sequence is not a chromosome because important chromosomal structures must be present: telomeres, centromeres, nucleosomes, euchromatin and heterochromatin. At least these structures are present in linear chromosomes in eukaryotes, not in the circular chromosomes of most bacteria. Although linear chromosomes probably have advantages, they come with problems: replication of linear chromosomes presents a problem as it leads to gradual loss of the terminal telomeric regions, the telomeres.
    
    • heterochromatin and euchromatin: Giemsa staining reveals banding patterns with darkly stained heterochromatin and lightly stained euchromatin bands in chromosomes. Euchromatin is transcriptionally active and heterochromatin is transcriptionally silent. Functional genes are located in lightly stained euchromatin bands. This is a nonrandom pattern. If genes were located in heterochromatin, they would not be transcribed. These facts were known in 1994.

      telomeres (white dots), centromeres (red dots) (Science 22 April 2011)

    • Telomeres: Telomeres are structures at the ends of chromosomes that contain a series of non-coding DNA repeats, and which become shorter themselves but protect the coding regions from damage. Human telomeres are several kilobases of repeated sequences of DNA bound by specialized protective proteins. A peculiarity of the DNA-replication mechanism causes telomeres to shorten as cells divide. Sometimes the enzyme telomerase can replenish the lost DNA. If telomeres get too short, through aging or because telomere maintenance goes awry, cells can stop dividing. The protection conferred by telomeres is a fundamental biological mechanism present in nearly all animals and plants (119). 'Independently born' organisms (if they exist) have at best telomeres with a random length, simulating cells and chromosomes of random age –from old, average to young. That means many wil not be able to complete replication.
      
    • Centromeres are defined as pieces of non-coding repeated DNA with variabel DNA sequence that function as the site of spindle attachment at cell division (mitosis and meiosis). They are essential for equal chromosome separation during cell division. Remarkably, centromeres are inherited epigenetically (389). That means DNA sequence does not determine the identity of the centromere. This implies that ultimately the centromere is inherited from a previous generation. There is no previous generation in the Independent Birth of Organisms hypothesis.
      
    • Histones are proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. Without histones human DNA could not fit in the nucleus because it would be too long. DNA without histones could certainly not enter mitosis. Histones are highly conserved in eukaryotes, so random origin is virtually excluded. Histones have also a function in gene regulation. Along with histones come more than 20 histone modifiers, chaperones and other regulators. Important question: Where do histones come from in the independent origin scenario? It does not help that histones are encoded in the DNA, because how are they supposed to be transcribed into mRNA and translated into protein? (see below)
    • Nucleosomes consist of DNA wrapped two times around small, globular histone octamer particles. They form the fundamental repeating units of eukaryotic chromatin, which is used together with condensin (359) and topoisomerase II to pack the large eukaryotic genomes into the nucleus while still ensuring appropriate access to it. Already in 1987 a publication appeared pointing out the relation between chromosome structure and gene expression.
      "Since 1968, we have learned that DNA wraps around histones, packing ~10² base pairs into the 10^–8m nucleosome. We also know that individual chromosomes occupy distinct subnuclear volumes called chromosome territories which pack ~10⁸ base pairs into 10^–6 m (243).
      
      

      ©Science 28 Jul 2017: ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells.

      
      
    • sex chromosomes: eukaryotic genomes come in two forms: male and female genomes. Males have a unique chromosome that females don't have: the Y-chromosome. Because males have only one X-chromosome and females two X-chromosomes, a mechanism is necessary to ensure genes on the X-chromosome are expressed in the right levels. Dosage-insensitive genes are those that function perfectly well when present as a single copy. By contrast, two copies of dosage-sensitive genes are required for normal health. (dosage compensation, X-inactivation).
      
    • Linear chromosome: Here is the fundamental problem for the theory of independent origin: why should the most complex chromosome type, the linear chromosome, with all its problems, arise spontaneously in stead of the circular chromosome? For example: why don't humans have 46 circular chromosomes? Or why don't humans have one big circular or non-circular chromosome? On the other hand, evolution theory needs to explain the evolution of the linear chromosome (120).
    
    

(2) DNA and chromosomes in their biological context

Here is the paradox in a nutshell: To produce a protein from DNA specific proteins are needed. It does not help that those proteins are encoded in DNA. Surely, every necessary protein could be encoded in DNA. The point is that DNA needs to be transcribed and translated (250). That requires enzymes to be present in the first place. 'The central dogma of molecular biology' states that genetic information encoded in DNA is transcribed to mRNA (by RNA polymerases (321)), and mRNA is translated to protein (by ribosomes, and 20 different tRNAs which are made by 20 different aminoacyl-tRNA synthetases). Since RNA-polymerase is a protein itself, it needs to be present before it can be produced (275). This is certainly impossible for the first 'independent organism'. This alone is fatal for the theory of independent origin. This is why the origin of any organism from naked DNA is impossible! This is also why scientists concluded that there must have been a RNA-world before a DNA-protein world. This is also why even giant viruses with all the genes for mRNA synthesis, etc. still depend on living cells for their reproduction (see: The elephant in the room).

Here are three examples of this vicious circle: Transcription: Transcription: a DNA segment is copied into mRNA by RNA-polymerase. RNA-polymerase is an enzym, which is a protein. That protein is encoded in DNA. The synthesis of RNA-polymerase starts with transcription. For transcription of the RNA-polymerase gene a RNA-polymerase enzym is required: vicious circle. (228). See: Transcription. Translation: "Translation is probably the most complex biochemical cellular process, needing more than 120 different molecular elements ranging from messenger RNA to ribosomes and their many protein and RNA accessories. ... even the smallest of cellular organisms (Mycoplasma genitalium) need a minimum of 90 different proteins for translation and about 30 for DNA replication." (185), (250). The eukaryotic ribosome is composed of 79 ribosomal proteins. "More than 200 assembly factors and small RNAs are needed to synthesize ribosomes in the nucleolus. Ribosomes are absolutely essential for life, generating all cellular proteins required for growth. Complete loss of any single ribosomal protein often leads to death of the embryo in mice" (317). (See: Translation). Ribosomes are assembled from (382): 4 distinct ribosomal RNA (rRNA) molecules 80 different proteins, which form small and large subunits more than 200 assembly factors Replication: Every cell division requires DNA replication. DNA does not 'self-replicate'. "Nude DNA does not self-replicate" (394). Replication enzymes (DNA polymerases) are requited. At least 15 DNA polymerases operate in human cells. Human DNA polymerases are 900-1000 amino acids long (2700 - 3000 base pairs). The minimum set of proteins required to initiate DNA replication in eukaryotes (Saccharomyces cerevisiae) is 16 proteins (351). "The work of a generation of biochemists, notably Arthur Kornberg, has shown that it takes dozens of protein complexes, each involving many proteins to accomplish this [replication]. They can be thought of as complex components of several giant molecular machines, which synthesize the new DNA, check it for errors, and pass it on for further interactions which package it in chromosomes." (264). The polymerases responsible for replicating nuclear DNA are at least 100-fold faster and nearly 1,000-fold more accurate than polymerase η which is involved in DNA repair caused by ultraviolet light (278). See: Replication.

1. A DNA sequence is nothing without proteins:
   histones, condensins, cohesins, DNA polymerases, replisome, primases, telomerases, topoisomerases, helicases, DNA gyrase, ligases, DNA glycosylase, deaminases, release factors, Ribosome Recycling Factor, nuclear receptors, chromatin remodellers, histone demethylases, DNA repair enzymes, transcription factor, repressor, activator, spliceosomes, splicing regulatory proteins, nucleases, DNA methyltransferases, ribosome, RNA polymerases, RNA-binding proteins, Origin recognition complex (ORC), Chromatin Assembly Factor-1 (CAF-1), ...
   
   
2. A DNA sequence is nothing without RNA 18 Feb 12
   DNA can do nothing without RNA. In fact, DNA cannot even replicate without the prior formation of an RNA primer (270, p.66).
   
   
3. DNA specifies amino acids but does not synthesize amino acids 1 Feb 12
   DNA specifies the sequence of amino acids in proteins but does not synthesize amino acids. So, when there are no amino acids available (for example essential amino acids), protein synthesis is impossible. To synthesize 'non-essential' amino acids the cell needs specific enzymes. Those enzymes can only be produced when the right amino acids are available. This is because enzymes are a sequence of amino acids.
   
   
4. DNA does nothing without ribosomes 22 Mrt 24
   "For if DNA is data then it can't go anywhere, or do anything, without a machine to process it. The ribosome is that machine." (435).
   
   
5. DNA sequence is not sufficient to produce proteins 13 Jul 11
   About one quarter to one third of all proteins require metals to carry out their functions (metalloproteins: iron, copper, magnesium, cobalt, zinc, molybdenum, vanadium, manganese, nickel, selenium). For example, iron and copper are present in virtualy all enzymes and in some proteins that interact with oxygen (215). However, metals are not coded by DNA! So, protein specification by DNA is incomplete. Furthermore, most of the Mg2+ in a cell is bound to DNA, to RNA, to the cellular energy carrier ATP or to enzymes, and acts as an essential cofactor for these molecules. Mg2+ is not in the Sequence.
   
   
6. DNA is an archive (1). It must be read to have any effect 5 Jul 19
   DNA is like a book. The book does not read itself. It needs a reader. The right piece of DNA must be read (transcription) on the right time in the right quantities in the right cells. The transcript must be translated. There must be a
   • Transcription Code:
   • Translation Code:
   • Splicing Code:
   • Epigenetic Code:
   
   
7. DNA is an archive (2). It must be read in the right place and time 4 Jul 22
   In a multi-cellular organism (plants and animals) genes must be transcribed in the right place and time especially and crucially in the development of the embryo (391). Also genes must 'know' if they are in a female or male body.
   
   
8. The Transcription Code 18 Feb 11
   The genetic code is not the only code. The processing of the information of DNA starts with transcription, which requires:
   • each gene has its own promoter element (contains a conserved gene sequence called the TATA box) and enhancer element(s)
   • initiation codon: AUG is an initiation codon or start codon. The next gene does not start right after the stop codon, so an initiation codon is needed. Senapathy ignores this.
   • termination codon UAA that stops transcription.
   Where does the Transcription Code come from? It is not random. Furthermore, there is a transcription factor binding code within (!) the protein coding part of a gene (324). See also: 'Sequence basis of transcription initiation in the human genome' (437).
   
   
9. The Translation Code 30 Mar 12
   
   • Kozak consensus sequence is a non random sequence which occurs on eukaryotic mRNA and plays a major role in the initiation of the translation process.
   • ribosomal binding site (RBS) is a non random sequence on mRNA that is bound by the ribosome when initiating protein translation.
   • Internal ribosome entry site (IRES) is a nucleotide sequence that allows for translation initiation in the middle of a messenger RNA (mRNA) sequence as part of the greater process of protein synthesis.
   These are all nonrandom sequences and therefore lower again the probability of spontaneous origin.
   
   
10. The Histone Code 4 Oct 11
    The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends. Together with similar modifications such as DNA methylation it is part of the epigenetic code. (see Epigenetics below)
    
    
11. The Splicing Code 18 Feb 11, 9 Mar 11
    The very existence of introns requires splice site recognition: the border between intron and exon. So, Senapathy simply assumes splicing machinery when talking about introns and exons. This is the splicing code. Senapthy knows that "The sequences around the junctions of exons and introns are highly conserved" (p.549). How is that possible in random DNA? Where does it come from? Why that specific universal splicing code? The splicing sequence is in DNA, but that can only be 'a code' if specific splicing proteins recognize that sequence. The Splicing machinery must match the universal splicing codes in DNA. So, it does not solve the problem of the origin of split genes to search for splicing codes in random DNA. Of course one will find it in random DNA. The point is, however, that the splicing code is not random, so where does it come from? The spliceosome is a very complex ensemble of five snRNAs and about 200 proteins, so cannot arise from scratch. Furthermore, alternative splicing implies different proteins in different cell types. Furthermore, it has been shown that more than 20,000 unique Single Nucleotide Variants, SNVs, likely affect splicing (349). In addition to splicing, eukaryotes possess elaborate mRNA surveillance mechanisms, in particular nonsense-mediated decay (NMD), to assure that only correctly processed mature mRNAs are translated (170).
    There are two splicing codes: exonic splicing sites and intronic splicing sites. The exonic splicing sites implies a dual code because a piece of DNA encodes a protein and a splicing signal at the same time (303). There maybe a third function: nucleosome positions bias certain synonymous codons.
    All this effectively blocks the origin of splicing from scratch.
    
    
12. The Poly(A) Code 18 Feb 11
    The information in DNA is modified before it is used. No equivalent to poly(A) or the caps are in DNA and these are added to the mRNA (Polyadenylation). Therefore, a DNA sequence is not enough. The mRNA is modified. This is crucial for exporting mRNA from the nucleus to the cytoplasm. Alternative polyadenylation can also shorten the coding region, thus making the mRNA code for a different protein. Again: the information in DNA is not enough.
    
    
13. The Epigenetic Code: imprinting

    "The major problem, I think, is chromatin. What determines whether a given piece of DNA along the chromosome is functioning, since it's covered with the histones? What is happening at the level of methylation and epigenetics? You can inherit something beyond the DNA sequence. That's where the real excitement of genetics is now." (James D. Watson: 30).

    When the human genome was first fully sequenced, it was often described as the recipe for making a person. In reality, the genome is more like an entire cookbook that can produce hundreds of different cell types depending on which genes are switched on and off. That switching is accomplished using a vast suite of epigenetic marks (284).
    
    DNA-epigenetics (DNA methylation) and RNA-epigenetics (DNA/RNA methylation): is defined as the chemical modification of DNA and RNA that affects gene expression but does not involve changes to the underlying DNA sequence. As the emphasis in biology is switching away from 'The Sequence' and towards the mechanisms by which gene expression is controlled, epigenetics is becoming increasingly important (104). Cell differentiation is associated with selective DNA methylation. RNA marks are used by the cell to determine where, when, and how much of the protein should be generated (377).
    
    "Imprinting reflects competition between a mother's interests and a father's when it comes to gestating the offspring. A mother wants a fetus that doesn't grow too big, so she can survive the pregnancy. A father wants the opposite: a fetus that becomes a strapping baby and, later, a strapping adult who hoards resources and spreads his genes to new progeny. Essentially, imprinting means that in some places along the human genome –about 100 genes in all– the way DNA behaves depends on which parent passes it to the offspring." (357). This is all absent when a genome hypothetically originates de novo from a primary pond. Methylation marks are created and removed in the egg, sperm and fertilized zygote (390).
    
    

    'Writers' add chemical marks to the DNA or to the histone proteins that DNA wraps around. ©Nature. (285) (modified).

    ©Nature (click to enlarge) Epigenetic processes are essential for packaging and interpreting the genome, are fundamental to normal development and are increasingly recognized as being involved in human disease. Epigenetic mechanisms include, among other things, histone modification, positioning of histone variants, nucleosome remodelling, DNA methylation, small and non-coding RNAs. (Nature, 7 Aug 2008).

    Much of a cell's identity is determined by modifications to chromatin, which comprises DNA and the proteins that bind and package it. Epigenetic instructions, in the form of chemical marks that cling to chromatin, tell cells how to interpret the underlying genetic sequence, defining a cell's identity as, say, blood or muscle. The marks serve as instructions that are passed down as cells divide, providing a sort of cellular memory to ensure that skin cells beget other skin cells (285). Methylated cytosine (5-methylcytosine), often referred to as DNA's fifth base, makes up a subset of nucleotides in the mammalian genome (121). It can regulate tissue-specific gene transcription, without affecting the genetic blueprint. Cytosine methylation may function as a memory module of cell identity and developmental state.

    
    Two epigenetics examples:
    1. DNA methylation is essential for the survival of the embryo. Two studies of mouse embryogenesis now show that transmission of DNA methylation from gametes is predominantly maternal. Mouse embryos need maternal imprints for normal development.
    2. FBHM (Familial Biparental Hydatidiform Mole) is a recessive disorder in humans that results in repeated pregnancy loss due to a failure to establish maternal imprints at multiple loci throughout the genome (227).
       
    DNA of human sperm is highly methylated and that of eggs moderately so. There is a massive loss of DNA methylation from most of the zygote genome immediately after fertilization in human embryos: the erasure of epigenetic memory (337). However, specific DNA methylation appears to be obligatory in plants and vertebrates (eukaryotes!) (298). That's the end of independent origin theory. Furthermore, DNA methylation is used for repressing expression and preventing further expansion of repetitive DNA elements.
    
    
14. A DNA sequence does not survive
    

    "Any theory postulating that genes [!] may have emerged randomly and then waited to be used are fundamentally wrong, especially in a world dominated by the deleterious effects of the second law of thermodynamics. Genes had to have a functional meaning from the very beginning or they would have vanished soon after they emerged." (53).

    Please note, this applies to genes. Let alone to genomes. Furthermore, phenotypic effects of DNA are ignored: RNA-editing changes the sequence, and so the phenotypic effect. With no RNA-editing in the primary pond, the DNA sequence would probably not survive for this reason alone.
    
    
15. 1 Aug 2014 A DNA sequence is not chemically stable outside a living cell 
    
    DNA is stable enough to function as a carrier of heredity. However, DNA degrades naturally after an organism dies. DNA degradation is a process by which DNA breaks down into smaller fragments. Environmental factors such as sunlight, heat, and humidity can increase the rate of degradation. Further, Cytosine deamination takes place. DNA outside a living cell has a half-life of 521 years. That means that after 521 years, half of the bonds between nucleotides in the backbone of a sample would have broken; after another 521 years half of the remaining bonds would have gone; and so on (339). This has negative implications for the independent origin of DNA.
    
    
16. 7 Oct 2015 A DNA sequence is not chemically stable inside a living cell 
    

    "DNA is an extremely stable molecule that can be immensely long" (page 216, chapter 6)

    In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl (409) demonstrated that under physiological conditions DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA. Before Lindahl, nobody really considered the idea that DNA requires active engagement by a set of housekeeping processes to keep it in a stable state (353).
    
    
17. A DNA sequence is nothing without a nucleus
    Cellular DNA is usually found in the nucleus. It is rare to find DNA outside the nucleus, in the cytopla (434). The defining property that sets eu-karyotic cells apart from pro-karyotic cells is the nucleus (wiki). "Genomes are more than linear sequences. We usually think of genomes abstractly as one-dimensional entities that are purely defined by their linear DNA sequences. In addition to the complex arrangement of the genetic information itself, the cellular factors that read, copy, and maintain the genome are organized in sophisticated patterns within the cell nucleus. Specific nuclear processes such as transcription and replication occur at spatially defined locations in the nucleus." (Tom Misteli: 177, 178).
    
    
18. 31 Aug 2022
    All animals have 2 genomes. All plants have 3 genomes.
    A nuclear genome does not function without a mitochondrial genome. They depend on each other. The cell needs mitochondrial genes and mitochondria need nuclear genes. A random mixture of nuclear and mitochondrial genes certainly will fail 393b. Nuclear genes encode mitochondrial proteins. Mitochondrial genes have been transferred to the nuclear genome during evolutionary times (392, 393).
    These facts alone falsify the theory of Independent Origin. Above that mitochondrial DNA is inherited strictly from the mother. That means that all hypothetical 'male genomes' are doomed. Hypothetical 'female genomes' are doomed without species-specific mitochondria. A mature oocyte has nearly half a million copies of mitochondrial genes.
    
    
19. A DNA sequence is nothing without a cell
    Remarkably, in the Appendix Senapathy knows:

    "Usually, an organism starts its growth from a single cell" (p. 536)

    But if you start with naked DNA, how do you get from DNA to a cell? That is: membranes, mitochondria, ribosomes, nucleus, nuclear membrane, centrosome, ATP (energy). (See further details: par 7 Genome-centered approach).
    • Cell division (mitosis): from the first animal or plant genome a body must be created. That means millions of cell divisions. Chromosomes do not only create an organism, they are duplicated just before each cell division. "Chromosome segregation must be executed with high fidelity so that the mother cell and the daughter cell that arise from division receive precisely the same DNA content". Otherwise aneuploidy will result. Comparing the length of metaphase chromosomes to that of naked DNA, the packing ratio of DNA in metaphase chromosomes is approximately 10,000:1 (Nature). Therefore, central to the problem of segregation is the issue of packaging." (Nature).
      Mitosis is a complicated process in which about 625 genes are involved (Nature, 2010). In 2017 the number of genes having a role in cell division was 1295 genes (361).
      The spindle apparatus is the structure that separates the chromosomes into the daughter cells during cell division. Without spindle no cell division. The kinetochore is a complex machinery composed of more than 100 proteins through which chromosomes attach to the microtubules that form the spindle apparatus, which allows chromosome segregation. (see above: 'A DNA sequence is nothing without proteins').
      In other words: "To achieve accurate segregation, chromosomes rely on a specialized region known as the centromere. The centromere recruits the kinetochore, a proteinaceous macromolecular structure that forms attachments to the microtubules of the mitotic and meiotic spindles. Together, centromeres and kinetochores are the central players in chromosome segregation." (413).
      Proteins involved: separase, cohesin, etc.
      Conclusion: many non-random proteins must be present before a cell-division can happen. See Elephant in the room.
      
      
    • Embryonic Genome Activation:
      At fertilization, the animal genome is inactive, and the earliest stages of development are driven by pre-existing proteins and RNA transcripts that have been stored in the egg. As the fertilized egg divides into two cells, developmental control is gradually handed over to the embryo. The pre-existing RNA (known as maternally loaded RNA) is degraded, and the embryonic genome (called the zygotic genome) is activated (427). Only on the third day the human embryo, at the 8-cell stage, starts reading its genome (Embryonic Genome Activation). Before that moment transcripts can be detected in the embryo, indicating maternal deposition. But that is impossible for 'independently born organisms' because they do not have a mother and consequently no maternal RNA (352).
      Curiously, in the Appendix Genetics Primer page 560–561 he writes:

      "Some maternal factors (factors from the mother) or maternal genes can in some cases influence development from outside the embryo."

      So, he knows! But, he completely misses the fact that the first 'independetly born organisms' simply have no mothers! (14 Jun 2023).
      
      
20. A DNA sequence is nothing without microbes: "Animals grow up under the influence of their microbes, not just the blueprints encoded in their genomes. Microbes play a role in development. The bodies and immune systems of animals ranging from tsetse flies to mammals mature properly only after exposure to bacteria. The larvae of some marine worms metamorphose into adults only when they encounter bacterial molecules. (350). 15 Jan 2015
21. A DNA sequence is nothing without an organism: parts of the DNA sequence (genes) must be expressed at the right time and place in the right quantities in order to develop an adult from one cell and maintain life als an adult. This called positional information (Lewis Wolper). DNA itself does not contain positional information. To achieve this positional en temporal gene expression, proteins that control such processes have to bind to specific places in the genome. There is evidence that ageing entails a gradual drift towards more random patterns of gene expression, which might cause organ/tissue failure. There are millions of ways to express genes at the wrong time, place, quantity or sex. Furthermore:
    • other genes in the genome influence the function of a gene
    • the function of the gene product must be in accord with the laws of biochemistry (energy production, protein folding, catalysis, prevention of protein aggregation). Some proteins cannot fold without the help of other proteins, called chaperones, so that means: genes cannot function in isolation, they need other genes.
    • DNA must be protected from damage: right from the start DNA must be protected from damage (mutation). Indeed: a very complicated DNA-repair system exists. Furthermore, DNA must be faithfully duplicated (replication) with the help of specialized enzymes. It is highly improbable that they arose by chance.
    • a sequence of DNA is meaningless without the correct ecological context, that is biological and nonbiological (the physical conditions of the earth: temperature, atmosphere, climate, gravity, water). See: The genome is blind.
    
    
22. The interaction and interdependency of nuclear and mitochondrial genome: Interactions between the nuclear genome and mitochondrial DNA are essential for proper cellular functioning, but incompatibilities between the two can lead to compromised development and fitness. Despite having their own genomes, mitochondria don't make many of their own proteins; most are synthesized in the cytosol by cellular equipment encoded in the nucleus. Thus, the interactions of mitochondrial and nuclear DNA are critical to cellular life (318) 26 Sep 2013.
    
    
23. A DNA sequence is not an organism: an eukaryotic organism contains multiple separate genomes. See: separate page. Explaining the nuclear genome is not enough.
    
    
24.   22 Jul 2019
    There is no human genome!
    There is no such a thing as 'the human genome'. A human genome is either female or male. For humans: 46XX (female), 46XY (male). The Y-chromosome harbors male-specific genes. The genetic difference between men and women is 15 times greater than between two men or two women. (378). A males gets his X-chromosome from his mother. A female from her father and mother. Above the DNA sequence itself, there is different gene expression between the sexes in all tissues and organs in the rest of the chromosomes (autosomes).
    
    
25. 20 Nov 2022
    A human genome does not guarantee a healthy individual: There are over 6,000 known genetic disorders in humans (397). Each of those produce a diseased or handicapped person. When produced in the primordial pond they will not survive and reproduce. End of story.
    
    
26. A computer generated DNA string is a virtual thing, see: here.
    
    
27. The limits of a Genome-centered approach: see § 7

1. origin of DNA: a chemical problem
2. origin of genomes: a biological problem
3. The origin of species: Darwin's problem

"Even the simplest cell needs DNA, amino acids, nucleotides, proteins and other molecules to construct the structure of the cell such as cell membranes, and cellular machineries such as ribosomes. The cell needs enzymes to synthesize these molecules and metabolize nutrients. Without such absolutely basic things, no living cell can ever come into existence." Note 1 of Chapter 7, in NOTES AND REFERENCES page 596.

"Some form of translational machinery, far more complex than a single enzymatic function, must have come into existence in the primordial soup to switch from non-DNA-coded to DNA-coded genetic machineries." page 216 Chapter 6.

"Numerous metabolic enzymes are required for the structures and functions of even the simplest living cell, because these are required for the metabolism of the basic chemicals which are required for the life of any living system." page 427 Chapter 9.

"It is an all-or-none-law that if complete genes existed in the random primordial DNA sequences, then complex machineries and complex cells should be formed;" p.284 Chapter 7.

The genome-centered and information-centered approach

“Thus, the genome is the master of the cell and the organism.” (p.551, Appendix - Genetics Primer)

“Replicators are the units that survive (or fail to survive) through the generations. Vehicles are the agents that replicators programme as devices to help them survive. Genes are the primary replicators, organisms the obvious vehicles.” (291)

“DNA is famous as the instruction manual of life — the multi-billion-base-pair data tape that directs how a fertilized egg turns into the specific cells, tissues and organs” (294).

eukaryotic cell (source) (see wikipedia for explanation)

According to Senapathy, p.552 Please note: except mitochondria, there are no internal structures in the cell and no indication of DNA in mitochondria. See: Endosymbiosis theory refutes Senapathy, § 28 and 30.

• The ribosome is an RNA-protein complex performing protein synthesis in all living cells. The emergence of the ribosome constituted a pivotal step in the evolution of life. This event happened nearly four billion years ago.
• The centrosome (wiki, 55,56) is inherited from a mother cell. Upon cell division, each daughter cell receives one centrosome.
• The mitochondrion is inherited from the mother(!); it is not coming from the environment (!). There is an interdependency of mitochondrial genome and nuclear genome. Where does the mitochondrion come from in Senapathy's theory? (408). How could the interdependency be explained? Furthermore, mitochondrial DNA has prokaryotic origins and has a circular form. Prokaryotes can not originate from random DNA according to Senapathy himself (see: Endosymbiosis refutes Senapathy).
• other organelles: Rough endoplasmic reticulum, Golgi apparatus, etc.

"Critics of gene theory continue to emphasize that only a cell can make a cell, and that plant and animals emerge from eggs, not genes" (38)

"strange claim by some of the world's leading molecular biologists that the human genome is the holy grail of biology is a stunning example of a biology that has no genuine guiding vision"

"One of the main arguments I will make in this book is that structures resembling microscopic soap bubbles were an absolute requirement for life to begin, as essential to the process as the assembly of genes and proteins". (David Deamer (2011) 215, p.3.)

Not by genes alone Do genes code the organismal form? Not quite, says evolutionary biologist Massimo Pigliucci: "Genes by themselves do literally nothing. Organisms do not begin with a bunch of genes that generate everything else: they need a set of environmental conditions, as well as the inheritance of materials and extra-genetic information from the previous generation. From the point of view of causal analysis, genes may be said to be a necessary but far from sufficient condition for the development (and evolution) of organisms." (Original link: life.bio.sunysb.edu/ee/pigliuccilab/bookclub/ does not exist anymore.)

Not by DNA alone "Today, the view that biological information is transmitted from one generation to the next by the DNA sequence alone appears untenable. There is increasing awareness that non-genetic information can also be inherited across generations." Étienne Danchin et al (2011) Beyond DNA: integrating inclusive inheritance into an extended theory of evolution, Nature Reviews Genetics 12, 475-486 (July 2011).

A DNA sequence is meaningless "A DNA sequence, by itself, is meaningless. The information in the double helix is interpreted through its interactions with the rest of the cell." Barton et al (2007), EVOLUTION, p.381.

A DNA sequence is an archive "An organism is not a linear script in a DNA language we have learned to read. In fact, such a simplification is a shocking distance form the truth." "Without RNA, a cell would be all archive and no action". Michael Yarus (2010) Life from an RNA World, Harvard University Press, p. 97.

A DNA sequence is dead "Despite its obvious importance to life, biological energy receives far less attention than it deserves. According to molecular biologists, life is all about information. (...) Life without energy is dead" Nick Lane (2005) Power, Sex, Suicide, p.68.

Genes don't do anything "Critical to my appreciation of genetics was the understanding that by and large genes don't actually do anything at all." Lisa Seachrist Chiu (2006) When a Gene makes You Smell Like a Fish and Other Tales about the Genes in Your Body, p.2.

DNA is an inert database "DNA isn't life. It doesn't even leave the nucleus of the cell. A whole army of proteins is needed to unpack, edit, and execute the information it contains. Without this apparatus, DNA is but an inert database, full of errors and repetitions. To grasp the nature of life, we must move away from our obsession with genes alone." front flap text of Denis Noble (2006) The Music of Life. Biology Beyond the Genome (216)

Every gene needs an environment "We now know that there is no such thing as a gene that acts in isolation and that every gene needs an environment --whether the environment is the presence of molecules made by other genes, signals generated internally within the developing nervous system, or electrical activity transduced from the external world. The genes of brain development are impressively environment- and experience-dependent." Mriganka Sur (2008) NEUROSCIENCE: The Emerging Nature of Nurture, Science 12 December 2008: Vol. 322. no. 5908, p. 1636

Mysteries of the Cell "We live in the golden age of genetics, but the fundamental unit of biology is still arguably the cell." John Travis, Mysteries of the Cell, Science 25 November 2011

Processes of Life "Beyond doubt, Dupré emphasizes, the perpetuation of life from one generation to the next requires much more than simply the passage of DNA. He concludes that genomes do not merely store information. Because of their constant dynamic interaction with other constituents of the cell, their capacities depend not only on their sequence of base pairs. More important, those capacities are determined by the systems of which the DNA molecules are only part." Review of Processes of Life. Essays in the Philosophy of Biology by John Dupré, Oxford University Press, 2012 in Science 17 Aug 2012.

DNA is not just a database "It is tempting to regard this famous molecule as just a database containing the algorithm for constructing an organism. But DNA is also a physical object that constantly bends, twists, and interacts with other biomolecules." Philip C. Nelson: Spare the (Elastic) Rod, Science 31 August 2012

DNA does not 'play itself' Does this sheet music play itself? Of course not. Sheet music is coded music, but it needs an interpreter to become music. Even a pianola roll does not play itself! You need a pianola to play the music encoded in the paper roll. A pianola roll without pianola is dead. Also, DNA does not 'play itself'. It needs cell machinery to 'play itself'. DNA without a cell is dead. Would a paper roll with random holes encode 'random music'? That is certainly possible, but still a pianola is required to play it. And the pianola itself does not spontaneously arise out of random parts.

Genetical determinism "Scientists have long since abandoned any concept of biological determinism. It has now been proved beyond doubt that although our genes are fixed, their expression is highly dependent on what our environment throws at us." Nature editorial, 'Life stresses', 11 Oct 2012

22 Nov 2012 A DNA-centric viewpoint "After the Second World War, biology in the West moved away from thinking of the cell in physicochemical terms, towards a reductionist molecular-biology approach, with a DNA-centric viewpoint. (...) Not surprisingly, cold-war divisions led many US scientists to dismiss Oparin. The Nobel laureate Hermann Muller, who thought that life originated as a gene, criticized the poor status of DNA within Oparin's picture of early life." 'In Retrospect: The Origin of Life', Nature Books and Arts, 22 Nov 2012

13 Aug 13 The Hologenome "In this light, the phylosymbiotic microbiome (*) can be understood as an addition to the coadapted genomes of a host organism rather than an arbitrary amalgam. Linking the microbiome and host genome underscores the hologenome as a unit of evolution and blurs the lines between what biologists typically demarcate as the environment and the genotype of a species. Based on the mounting evidence for speciation by symbiosis, it is becoming clearer that a unified theory of evolution that considers the nuclear genome, cytoplasmic organelles, and microbiome as interacting components in the origin of new species is an emerging frontier for biology." (316). *) the microbial community relationships that recapitulate the phylogeny of their host.

27 Nov 13 The Philosophy of Biology "There is more in biology than nucleotide sequences, as there is more in language than letter sequences. ... Development is a complex process of which DNA is an important, but not the only, factor. ... Biology education should make clear that life requires not only DNA but also a complex cellular machinery." (322).

11 Dec 2013 Tibor Gánti: The Principles of Life "Consequently, a living system should necessarily comprise at least two systems, of which one is the controlling unit and the other is the controlled part. (...) It is naïve to believe that the genesis of life can be clarified by studying whether a program can be developed by itself. It cannot." (p.15.) "It has already been mentioned that the cytoplasm and the nucleus can only develop together: no multicellular organism can develop either from a nucleus alone or from the cytoplasm of an ovum without a nucleus. ... [similarly] an embryo cannot develop from the ovum if either its cytoplasm or its nucleus is missing, and no cell can operate without these either." (p. 17) (323). "This book is a polemic essay. A polemic essay against the onesided idea of biology having the genes in the center. ... Fate brought that I have to oppose again a dogma, against the dogma of omnipotent genes." (Contra Crick, 1989)

30 Jul 2014 The dual nature of life: information and energy "Life is not just a genetic entity. Genes by themselves do nothing more than salt crystals. Life is an open, cycling system organized by the laws of thermodynamics." Eric D. Schneider and Dorion Sagan (2005), Into the Cool. Energy Flow, Thermodynamics, and Life, p.24 paperback.

9 Aug 2014 Richard Lewontin: a critic of the DNA-centric view "The trouble with general scheme of explanation contained in the metaphor of development is that it is bad biology. If we had the complete DNA sequence of an organism and unlimited computational power, we could not compute the organism, because the organism does not compute itself from its genes. (...) Of course it is true that chimps look different from humans because they have different genes. And a satisfactory explanation for the differences need not involve other causal factors." Richard Lewontin (2000) The Triple Helix. Gene, Organism, and Environment, p.17. Note: (342)

1 May 2015 A review of: In Search of Cell History by Franklin M Harold "One theme in the book, which I happen to be partial to, is the implication that biologists have been overly fixated on DNA. We tend to think that, because variation in DNA maps onto variation in phenotype, genes control all aspects of living cells. However, the conversion of information in DNA into cell structure depends on the cell itself reading and interpreting the genetic information. And the cell has aspects of organization, for example membrane-bound structures and long-lived protein complexes, that are passed down from generation to generation without direct encoding in DNA. Genetic software requires cellular hardware (or should it be 'gelware'?). For these reasons, we should not be overly gene-centric when thinking about cell evolution, but should also give due weight to biochemical, energetic, and structural aspects of living cells. For example, I agree with Harold that a simplistic gene-first (RNA-world) model for the origin of cells is flawed. RNA molecules cannot replicate themselves–they need to be embedded in a chemical system that allows their information to be copied. Explaining the origin and perpetuation of this system cannot be laid simply at the feet of the RNA molecules themselves". (reviewed by David Baum)

5 Aug 2022 Life is at root a chemical phenomenon "For decades, biology has been dominated by information – the power of genes. The importance of genes is unquestionable, yet there is no difference in the information content of a living protozoon and one that died a moment ago. The difference between being alive or dead lies in energy flow, in the ability of cells to continually regenerate themselves from simpler building blocks. ... We do not merely inherit inert information in the form of genes – our inheritance includes this living metabolic network in the egg cell, a flame passed from generation to generation, without pause, right back to the emergence of life. ... Without the flame life is – dead" Nick Lane (2022) Transformer: The Deep Chemistry of Life and Death (Introduction).

4 Aug 2023 Without a cell, a genome doesn't mean much "Nevertheless, the gene-centric view has established a form of tyranny where genes reign supreme over not only our past and present but also our future." "But the genome is not actually a blueprint for an organism or its architect. Insofar as it contains any design, it is the design for another genome, not for an organism." "But without a cell, a genome doesn't mean much. For creatures ranging from a virus to a human being, it is cells that give meaning to those sequences of nucleic acids by translating stretches of them into proteins. It is cells that use those proteins to take care of and repair themselves. Most importantly, it is cells that work with other cells to construct an organism. The cell decides which genes are used for what purposes and when, rather than being at the mercy of the genes." "DNA cannot send orders to cells to move right or left within your body or to place the heart and the liver on opposite sides of your thorax. DNA cannot measure the length of your arms or instruct the placement of your eyes symmetrically across the midline of your face." (NOEMA magazine by Alfonso Martinez Arias) Alfonso Martinez Arias (2023) The Master Builder: How the New Science of the Cell Is Rewriting the Story of Life. See for example the end of chapter 1 NOT IN THE GENES.

Phylogenomics Ironically, the study of genomes, called genomics, is precisely the research field that enables biologists to construct the tree of life! The use of genomics to construct Darwinian trees of life is called phylogenomics. An example is: 'A Phylogenomic Study of Birds Reveals Their Evolutionary History' published in Science, 27 Jun 2008. According to the theory of Senapathy there can be no true tree of all birds, because there is no common descent of all birds. See also: Elizabeth Pennisi (2008) 'Building the Tree of Life, Genome by Genome', Science 27 June 2008: 1716-1717. See also: Phylogeography from Wikipedia, the free encyclopedia.

Everything you always wanted to know about sex, but were afraid to ask

1. Human body cells are diploid: one complete set of chromosomes from the father, plus one complete set from the mother. (95)
2. sperm and egg cells are haploid: 1 incomplete set of chromosomes.
3. a zygote is a fertilized egg: haploid egg + haploid sperm = diploid zygote.
4. humans have a diploid set of 23 pairs or 46 chromosomes in total
5. females have 23 identical pairs, including a X-chromosome pair, excluding the Y-chromosome
6. males have 22 identical pairs and one non-identical pair of a X-chromosome and a Y-chromosome. The Y-chromosome is about 1/5 the size of an X-chromosome (see photograph, and diagram: Fig. 2).
7. the Y chromosome contains the SRY gene, which triggers development of male sex organs (432)
8. human egg cells have always one X chromosome and sperm cells have either one X or one Y chromosome.
9. additionally female egg cells contain many mitochondria each containing 37 genes. The mitochondria are transmitted exclusively via the female egg cell.
10. X-inactivation: females have 2 X-chromosomes, one of the copies of the X chromosome is inactivated: this prevents females from having twice as many X chromosome gene products as males.

"The genomes were directly assembled into single seed cells, analogous to the fertilized eggs of sexually reproducing organisms" (page 5)
"male and female 'seed cells' lead to male and female individuals";
"Both male and female seed cells can be assembled";
"One can infer that it is not difficult to segregate the genes for a male or a female into a specific chromosome and in two different sex cells". (page 358)

"Perhaps among the organisms produced in the primordial pond, some had only secondary sex organs, but no genital organ to copulate; whereas other organisms would have the latter but not the former. Both the above situations may or may not have had the reproductive cycles of sperm/egg production. There could have been many seed cells producing individuals, with wrong combinations of male and female sex organs and secondary sex characteristics. Rarely, some seed cells will process all the three sets of genes for all these three functions - attractiveness by secondary sex features, copulation by genital organs, and reproduction by sperm/egg cycles. This is analogous to many seed cells giving rise to individuals with improper or incomplete organs, which will not survive. Only those individuals with the absolutely right organs will survive. Therefore, only one out of myriads of seed cells may form a viable organism. This may explain why it would have taken geological time for seed cells to be formed with genomes capable of producing viable organisms." (page 358-359.) (my emphasis) (97)

Can a male or female arise from haploid cells?

X     Y Fig 2. Human sex chromosomes (2)

why on earth are not all species haploid?

Possible objections I suppose Senapathy could come up with the following objections: (1) maybe millions of different genomes could produce humans. – This is not relevant. What is relevant that any genome must be produced in a male and a female form. That makes it impossible. (2) genes do not need to be in same position as the current positions to produce a human, so the probability to produce a human genome from random DNA sequences is very much higher. – Theoretically it seems quite possible that genes which are ordered in a different way on the human chromosomes would still produce a human being. However, paternal and maternal genes (alleles) have identical positions on chromosomes. That situation must be explained. (3) there are many variations of a gene that produce the same protein and many protein sequence variants produce the same enzymatic function. – This is right but not relevant because I only considered the positions of genes on chromosomes. Those chromosomal positions must match. (4) sex organs are generated by genes just as all other organs, so it should not be difficult (p.353). – Of course sex organs are generated by genes. That is not the point. The point is: what is the probability that male-specific genes come together on chromosome Y and that the sex-genes are expressed at the right time and the right place in the right sex, and that both genomes are identical apart from sex-specific genes, and both genomes are able to fuse and create a new individual?

Can a male or female arise from diploid cells?

Did prokaryotes arise from eukaryotes?

Fossil evidence refutes Senapathy

Endosymbiosis theory refutes Senapathy

"Some scientists have suggested that eukaryotes were formed by "endosymbiosis"... Although there exists some resemblance between mitochondrion and bacterial cells, the origin of the nucleus in the eukaryotic cell is still considered to be a total mystery." (p. 231).

"the contiguous genes of prokaryotes could only be derived from eukaryotic split genes by losing introns" (page 232 chapter 7)

Mitochondria contain DNA "Take the enzyme cytochrome oxidase, for example, which handles the final step of cell respiration. In mammals, the complex is composed of 13 subunits, 3 of which are encoded by mitochondrial DNA, and 10 by nuclear genes. If the subunits of cytochrome oxidase don't work together properly, electrons are not passed to oxygen and respiration fails, triggering the death of the cell." "The mitochondrial and nuclear genes adapt to each other within a population, and the process must happen quickly because the mutation rate is so high in mitochondrial DNA." Nick Lane, Nature 19 Nov 2009.

Chloroplasts contain DNA   15 Apr 2012 Several researchers proposed that chloroplasts evolved from bacteria (endosymbiosis) in the late 19th century on the basis of microscopic study of plant cells (246, p.44) and again in 1905 and 1907 (244). In 1962 Hans Ris and Walter Plaut demonstrated DNA in chloroplasts in plants (245). This is not an obscure publication, it has been cited at least 15 times between 1964 and 2011 (it is not known in wikipedia). In 1967 Lynn Margulis under the name L. Sagan concluded that not only chloroplasts, but also mitochondria evolved from endosymbiotic bacteria (246, p.44). In 1970 she published her paradigm-changing book Origin of Eukaryotic Cells. In 1978 Robert Schwartz and Margaret Dayhoff proved the endosymbiosis theory (248). Senapathy could and should have known all this in 1994. Land plant chloroplast genomes typically contain around 110-120 unique genes. Some algae have retained a large chloroplast genome with more than 200 genes (source). Second argument against Senapathy: chloroplasts are derived from free living cyanobacteria. That means those cyanobacteria must have existed before eukaryotic plants. This contradicts Senapathy's scenario in which bacteria evolved from eukaryota.

Bacteria and Archaea To complicate matters further, the Woesian revolution established that that prokaryotes, far from being a homogeneous group, actually consists of two genetically very different groups: Bacteria and Archaea (73, 114). Although Archaea superficially resembled bacteria (being single-celled and lacking a nucleus), Archaea have a distinctively different metabolism, cell wall, and transcription machinery. That means in Senapathy's theory both Bacteria and Archaea are supposed to have originated from eukaryotes. This is very unlikely.

All mammals require maternal care

© Lennart Nilsson (1990) Human embryo with umbilical cord. The umbilical cord is the link between mother and embryo and symbolizes dependency.

"When we consider the case of the independent birth of mammals, it is reasonable to think that a conglomeration of a large number of cells and biochemicals in the primordial pond could have formed an environment akin to that of the placenta and uterus of mammals. There, a seed cell can differentiate into an embryo and a full-grown offspring". (Senapathy, p.309 chapter 8)

©Antal Festetics, 1983

Common descent versus independent origin

similar species of a distinct creature millions of distinct independently-born creatures Fig 3. Senapathy, p.462

pheasants ducks dogs   cats   horses creation of basic types Fig 4. Paul Nelson (7)

"Our new theory does not dispute the occasional connections among different families within an order, or the more common connections among genera within a family or species within a genus." (page 454 chapter 10)

"many species within a genus usually connectable by evolution and many families within an order are sometimes connectable by evolution" (p.461 chapter 10)

"a common pool of genes in the same primordial pond" (p.455).

"slightly changed creatures could also be produced in the primordial pond by mechanisms of genome mixing and genome alteration and or restructuring" (p.455)

"We stated in the new theory that an already successful genomes could be used, in part or full, in the construction of the genomes of later born organisms." (p.419).

1. This is again contradicting independent origin;
2. If 'genome mixing' completely mimics common descent, then there is no observational difference of his theory and common descent
3. 'genome mixing' and 'in part or full' is arbitrary, too vague, too 'cheap', too 'easy' giving a maximum of freedom
4. it does not make sense that anything goes at the moment that genomes originate and millions of years thereafter all genomes are frozen (immutable)
5. It is impossible to refute such a theory. When showing evidence that refutes independence, Senapathy always can claim 'my theory can explain this by a common pool of genes and genome mixing'. We do not learn anything new about nature.

The role of randomness and improbability

"When the number of random events are large enough, the unbelievable will certainly happen" (p.332).

"the universal sequence pool of random DNA sequences totalling approximately to 10^30 nucleotides could have existed in the primordial ponds."

The role of natural selection

"Only one out of a very large number of "genomes" assembled into seed cells can become viable. (...) A creature born from a genome should be first physically fit in the environment. If not it dies at birth. If an ecological fit occurs for a physically fit organism, then it survives." (page 313 chapter 8)

Fig 5.

Fig 6.

Fig. 7. Later Senapathy produced this figure on the internet, demonstrating the extensive involvement of natural selection (although he disingenuously used different names such as 'failed trials', 'filter', 'window', 'pinhole'). He also uses the word 'natural selection', contradicting his book title "...Showing That Evolutionary Theories Are Fundamentally Incorrect."

The role of mutation: exploring DNA sequence space

"Mutations in a genome can only lead to normal individual variations, or to genetic defects, which are absolutely (28) useless for organismal evolutionary change"(p.46)

"the genome of every independently born creature is unique and unchangeable into that of another unique creature, and therefore is essentially immutable." (p.6)
"a snail can give rise to many different snail varieties, but never to a crab or a sea star." (p.46).

Adaptation. No random perfection!

"At the time of the birth of organisms, "random perfection" of organisms filtered the meaningful organisms from among the myriad mostly meaningless independently-born organisms. Those creatures that fit well with the physical environment survived while others perished. Among the physically fit immutable organisms, ecological fitness occurred by chance." (p. 204) (81).

Fig. 8. Is the match between the extreme long spur of the orchid and the extreme long tongue of the moth an accident? © image Sinauer 2005 (60)

Fig. 9. Which genome originated first: the humming bird genome or the flower genome? How could they survive and reproduce without each other? Is this mutual adaptation merely a genome accident? © image Sinauer 2005 (60)

©Scientific American Timema poppensis partially camouflaged on its host, coast redwood Sequoia sempervirens, California. Could both the genomes of these organisms originate randomly and yet the organisms look very similar?

"The genome is blind and cannot visualize the existing niches and environments. Therefore, millions of bizarre phenotypes must be produced in a species for the selection of one useful structure. (p. 89, see also p.75. my emphasis).

Ecology and the food chain

source

The role of time: the chronological order of life

Figure 11.1. The chronology and time table of the independent birth of organisms. Chapter 11: 'A New Look at The Fossil Record', page 497.

Current view of the Cambrian Explosion (541 million to 515 million years ago, that is a 26 million years period) indicated by red box. © Science (319) The figure shows that the Cambrian Explosion was preceded by the Ediacaran Biota (EB) and that a huge number of Classes, Orders, Families, Genera and Species originated after the Cambrian Explosion.

Senapathy's drawing of the origin of life (cover) with modern dates of origin added (66).

Dates according to mainstream science: first humans did appear 6-7 million years ago Old World Monkeys: 25 -33 million years ago first bats, dogs, weasels, elephants: 30 - 40 million years ago first placental mammals (rabbits, whales, rodents): 60 - 65 million years ago Brasilodon quadrangularis is the oldest mammal sofar: 225 million years ago first mosquitoes, honeybees: 65 - 70 million years ago first turtles: 65 - 190 million years ago first butterflies (Lepidoptera): 150 million years ago first birds: 155 - 165 million years ago first frogs, crabs: 135 - 190 million years ago first flowering plants appeared about 135 million years ago; grasses appeared around 94 million years ago first sex chromosomes (XY) appeared some 200 million - 300 million years ago first amniotes (land-living vertebrates): 310 million years ago first amphibians: 360 million years ago first tetrapods: 375 - 363 million years ago first insect fossil appeared 412 million years ago first land plants appeared 465 - 470 million years ago; plant with leaves appear with a delay of 40 million years; trees: 475 million years ago. fish with jaws appeared: 416 - 359 million years ago jawless fish appeared: 500 - 435 million years ago first multicellular animals: 635 million years ago eukaryotes: 1,000-1,300 million years ago cyanobacteria: 2.15 billion years ago stromatolites: 3.4 billion years ago putative fossilized microorganisms that are at least 3,770 million and possibly 4,280 million years old Potentially biogenic carbon preserved in a 4.1 billion-year-old zircon The reader is advised to have a look at: TimeTree: The Timescale of Life or: Deep Time. Interactive Infographic or: GSA Geologic Time Scale or: Geological time scale (wikipedia). There is detailed chronology of the first appearance of life forms in: Stearns and Hoekstra (2005) p.416-418.

source

Insect evolution © Nature 2 Aug 2012 (281)

Life got big after nearly 3 billion years of microbial evolution. Soft-bodied organisms of centimeter- to meter-scale first appeared 579 million years ago (180). Why the delay if every genome (mono-cellular and multi-cellular) was produced?

Chronology fact: plants The first plants on land were small and leafless. Plants with leaves appeared 40 million years later (72). Why don't leafless and leaved plants appear randomly in the fossil record? Why were plants (green algae) present in oceans 500 million years before plants colonized the land? Why do only land plants (especially trees) possess lignin? (277). What would be the use of enzymatic lignin decomposition gene in a genome of an organism born in the primordial pond? Why the chronological order of appearance? In Senapathy's genome-centered view the chronological and environmental context is absent. There is no possibility to answer questions why certain fossils are where they are. All organisms are born in the Primordial Pond and move out (see cover illustration of his book). But what about plants? Rooted and unable to flee from the Pond, plants drown and die. How could seedlings survive in the primordial pond? Could seeds germinate in a pond at all? And how do get from naked DNA to a seed anyway? Example: the desert-dwelling tobacco species Nicotiana attenuata has an array of mechanisms to survive severe environmental stresses including fire, herbivores and drought. However, could it survive in a pond? How does it move from the Primordial Pond to the desert?

Chronology fact: photosynthesis There ares two photosynthesis methods: C3 and C4 (used by 7500 plant species, mostly subtropical grasses, maize, sugarcane). The C3 method is optimal for high atmospheric carbon dioxide levels (100x today) and the C4 is optimal for low carbon dioxide levels. However, there is only one atmosphere and one primordial pond in Senapathy's scenario. Data support the view that the C3 system arose more than 2800 million years ago under high carbon dioxide levels, the C4 system arose as an adaptation to low carbon dioxide levels about 30 million years ago (72). If both systems were produced by the primordial pond, then the primordial pond must have existed from 3 billion years ago up to 30 million years ago. Unlikely as it is, it still does not explain why it produced the systems in that chronological order and why with such a huge time interval. See also: § 22 Incompatible primordial ponds.

Chronology fact: Great Oxygenation Event Great Oxidation Event (appearance of free oxygen O2 in Earth's atmosphere around 2.4 billion years ago) is believed to have followed the development of oxygenic photosynthesis by ancestors of modern cyanobacteria. Cyanobacteria have played a central role in the evolution of life on Earth, both by producing oxygen as a photosynthetic byproduct and by generating organic carbon, the major ecological energy commodity. DNA sequences from extant organisms bear an imprint of the GOE. Enzymes that bind molecular oxygen are more likely to appear in organisms that emerged after the Great Oxidation Event (155). However, it takes time to fill the earth's atmosphere with oxygen. To be precise: nearly 2 billion years! It was not until oxygen levels rose even higher, around half a billion years ago, that the oceans could support large multicellular eukaryotes that got their energy by burning food. In Senapathy's genome-centered view the chronological and environmental context is absent. See: Great Oxygenetion Event (wikipedia)

Chronology fact: Nitrogen cycle: bacteria first Proteins and DNA contain Nitrogen (N). The atmosphere of the earth contains enough nitrogen (78%), but remarkably, animals and plants can not use it. Only nitrogen-fixing bacteria (prokaryotes!) can use nitrogen from the air. (Some fixation occurs in lightning strikes). This imposes a chronological order: first bacteria, then plants, then animals. So, independent origin of animal and plant genomes is impossible. In Senapathy's genome-centered view the chronological and ecological context is absent. 2 Jun 11 See: Nitrogen cycle (wikipedia)

Chronology fact: chronology of sex Why on earth was there no sexual reproduction in the first half of the history of the earth? These are facts from the geological record. One does not need to be an evolutionist to accept them. On the theory of independent origin such groups of organisms should appear randomly in the history of the earth or why not all at the same time?

"We shall see that the new theory unifies all living organisms on the basis of the common universal gene pool of the primordial pond from which all distinct organisms were independently born." (page 378).
"Although millions of small and large ponds must have existed on the primitive earth" (page 214 chapter 6)

How does the theory of independent origin deal with the big extinctions and recoveries? The figure shows 5 major mass extinctions. Each is followed by recovery of the number of species. Overall, there is a clear increase in the number of species from 600 million years ago to today. This would require that primordial pond(s) must have been active continuously from 600 million years ago up to today. Figure: Nicholas Barton et al (2007) Evolution, p. 283.

The role of place: the biogeography of the origin of species

The clumpiness of morphospace

"What can be more curious than that the hand of a man, formed for grasping, that of a mole for digging, the leg of the horse, the paddle of the porpoise, and the wing of the bat, should all be constructed on the same pattern, and should contain the same bones in the same relative proportions?" (300).

C-value paradox: genome sizes are not randomly distributed over species.

• Why are genomesizes not randomly distributed over all living species? Why are they clumped? Why do genomesizes of birds and mammals not overlap?
• Why do all backboned animals have four fins or limbs, one pair in front and one pair behind? Why are all land vertebrates 'tetrapods' (4 legs), while none have six or eight legs?
• With a few exceptions, all mammals and birds are warm-blooded, and all reptiles, insects, arachnids, amphibians and fish are cold-blooded (218). Why is this, if they are independently born?
• Why do birds (of prey) have no teeth? It would be advantageous for larger pieces of food which cannot be swallowed in one piece. Why don't birds have a third pair of arms to handle their food? (since they can't use their wings for that task). Humans, apes, squirrels can use their hands for handling food. Why aren't there birds with internal gestation like mammals? Why are the chicks of all passerines (songbirds) altricial (blind, featherless, and helpless when hatched from their eggs)? Why are most passerines smaller than typical members of other avian orders? Why has the foot of all passerines 3 toes directed forward and one toe directed backwards? Why do birds embryologically start with paired oviducts, but one or the other side fails to develop (together with the corresponding ovary), and only one functional oviduct develops?
• What is the matter with genomes: birds have remarkably small genomes, averaging 1/2 to 1/3 of the size of typical mammalian genomes. Why should that be when all eukaryotic genomes arose independently? Small genome size is intriguingly correlated with flight. Bats, compared to other mammals, have small genomes, and flightless birds, compared to other birds, have larger genomes. (220). Why are introns and intergenic regions of birds half the size of mammals? (348).
• Why do only birds and insects fly, not frogs and mammals (except bats)? Why does not one of the almost 40,000 species of spiders fly? Why do all spiders have eight legs? Why do all spiders produce silk? Why are all spiders predatory and not herbivorous?
• What is the matter with genomes that there are twenty thousand species of birds and only twenty species of crocodile? (Mike Benton)
• What is the matter with genomes that insects are more numerous than any other type of animal, accounting for 80% of species?
• What is the matter with genomes that, unlike most animals (females: XX, males: XY), female birds are the heterogametic sex, having the equivalent of a human Y chromosome, called the W chromosome (females: ZW, males: ZZ) except ostrich and emu. Why is this property not randomly distributed over animals and birds?
• Why does the domain of mammalian carnivores contain a large cluster of cats, another of dogs, a third of bears, leaving so much unoccupied morphological space between? This is not expected on the random genome origin scenario.
• Why do each of the more than 1,000 species among one group of centipedes have an odd number of leg-bearing segments?

The primordial pond is a free lunch

"it is quite possible that transcriptional activity, a far simpler function (of RNA polymerase) could have been present in the primordial protein mixture." page 216, Chapter 6.

"genes for all these enzymes must have been available in the primordial pond's genetic sequences" (p.427)

Incompatible requirements for a primordial pond

The final refutation of independent origin

The origin of life

Spontaneous generation Senapathy's theory is a modern version of the theory of spontaneous generation. The Greek philosopher Aristotle believed in spontaneous generation of life. As late as the seventeenth century philosophers believed that mice, frogs, and eels could emerge from garbage, mud, and river water. According to Alec Panchen "Lamarck rejected common descent. Lamarck's theory was of continuous events of spontaneous generation with descent from generated organisms of innumerable parallel evolutionary lines. I know of no 20th-century evolutionist who accepts this view." (69). Indeed, Senapathy is no evolutionist. Louis Pasteur gave the final deathblow to Spontaneous Generation of bacteria. A very useful history of Spontaneous Generation is given by Iris Fry in The emergence of life on Earth (chapters 2,3,4).

"Such primitive proteins in the primordial ponds might have catalyzed a great number of reactions, albeit with poor efficiency. (...) This strongly supports the conclusion that the primordial pond must have had a great deal of catalytic activities."
"There can be no doubt that proteinoid-like catalytic activities could aid in the process of building long DNA molecules in the primordial pond.". (page 209 chapter 6).

1. the generation of simple organic molecules from inorganic molecules
2. chemical "evolution" to produce more complex organic molecules and primitive metabolic networks
3. the origin of self-replication and the creation of "genotypes"
4. compartmentalization and the creation of cells
5. the linking of genotype and phenotype
6. the origin of the genetic code
7. the takeover of early replication systems by one involving DNA

• DNA encodes the genetic information of proteins
• DNA replication and transcription requires proteins
• proteins cannot self-replicate (except prions)
• proteins cannot encode the information in DNA (Cricks 'Central Dogma')

1. a repository of information (in its sequence of nucleotides)
2. a catalyst

• See also: §25: What is life? in which I argue that one must first know what life is, before one can start to explain its origin.
• See also: Exploring Life's Origins. (animations!)

What is life?

1. a chemical motor (metabolism) that supplies energy to synthesize compounds necessary for the other 2 subsystems and is stable
2. a membrane which keeps the other 2 subsystems together, protects against dilution and is itself stable
3. an information-carrying subsystem (for example DNA) which enables reproduction of the 3 subsystems

Rerun the tape of life

PLOS ONE article

Figure 7A. The ROSG model. Origin of an eukaryotic gene from primordial random DNA.
ORF = Open Reading Frame, is DNA sequence between two stop codons.
Red: coding sequence is an exon. stop codons occurred too
frequently to allow functional proteins to be encoded in random DNA.
That's why processing is necessary. Please note there are no startcodons.

"It is remarkable that all the characteristics of random DNA are still essentially present in the split genes of present day intron-dense large genomes such as those in the human."

"The average exon length from the intron-rich genomes is about 170 bases whereas that expected from random ORF lengths is 60 bases. This may indicate that there has been a selection for longer exons within the allowed maximum ORF length of 600 bases for optimizing the frequency of suitable exon lengths."

The Nature Precedings articles

Conclusion

Agreements:

• Science should seek a natural explanation of the origin of life
• prokaryotes very rarely have introns, have high gene densities, low-entropy, compact, relatively small genomes (246, p.53, p.229).
• eukaryotes in general have many large introns, have low gene densities, have high-entropy, noisy, large genomes (246, p.53, p.229), 310, although the yeast genome is highly streamlined in comparison with those of most other eukaryotes (371), (287), (288).
• According to Laurence Moran (2023) (412) 3% of the sequence of an eukaryotic gene consists of exons and 97% of introns. That is roughly in agreement with what Senapthy estimated.
• it is mathematically 100% certain to find the sequence of any eukaryotic gene in computer generated random strings of A,T,C,G if the random sequence is long enough (262), (326)
• theoretically stopcodon statistics in random computer DNA logically follow from the premiss that there are 3 stop codons in 64 codons
• As pointed out by Paul Davies in an important article (384), in order to contain information, a DNA genome cannot have repeating patterns, that is it cannot contain much compressible information, it must be highly random in a information-theoretical sense.
• Any random DNA sequence of sufficient length will contain transcription-factor binding sites (309) and Random sequences rapidly evolve into de novo promoters (385).
• "Over the last decade, it has become apparent that new genes may emerge de novo from parts of eukaryotic genomes that were previously non-coding, such as intergenic regions" (376). It has been found empirically in Drosophila melanogaster that 59.9% of random 800-bp intergenic sequences were associated with a ≥ 150-bp single-exon Open Reading Frame (ORF) (328) which could theoretically produce a 50 amino acid long peptide.
• Recently it has been claimed by a genome researcher that a hundred million base chromosome of entirely random DNA will be transcribed, bound by DNA-binding proteins and the chromatin marked (289)
• Recently, it has been demonstrated for the first time that three human genes have arisen de novo from noncoding DNA (308), (411). but the human genome is not in a primordial pond! And 3 genes do not equal a genome!.
• some mainstream scientists use the concept "primordial gene pool" (233) ... so what?

Disagreements:

1. reduction of life to eukaryotes: neglecting the origin of prokaryotes
2. reduction of males and females to a sexless genome, ignoring male and female genomes and -chromosomes
3. reduction of eukaryotes to DNA sequences: genome-centric view of life, ignoring cells and (sex-)chromosomes
4. reduction of genomes to nuclear genomes, ignoring mitochondrial genomes (animals, plants) and chloroplast genomes (plants)
5. reduction of genomes to a random collection of genes, ignoring the probability of a complete viable genome
6. reduction of genomes to protein-coding genes ('protein-centric view'): ignoring everything else (an abundance of short and long noncoding RNAs, promoter regions, enhancer regions, transcription factor-binding sites, intergenic regions, histone modification, DNA methylation, chromosome-interacting regions, transposons, repetitive DNA)
7. reduction of genes to exons: discarding introns
8. reduction of exons to a sequence of 4 'symbols': reduction of biology to statistics, ignoring chemistry and thus the origin of the double helix
9. Recently, researchers showed that random DNA integrated in to mouse cells is transcriptionally inactive (436) refuting the idea that random DNA is transcribed and translated in eukaryotes.

Problems common to independent origin and evolution

Two major errors of independent origin:

virus

1. THE SEQUENCE IS NECESSARY AND SUFFICIENT TO CREATE AN ORGANISM

2. THE SEQUENCE IS NECESSARY AND SUFFICIENT TO EXPLAIN THE ORIGIN OF LIFE

spermium

Periannan Senapathy: thinking too far outside the box!

"Theorists in biology should realize that it is extremely unlikely that they will produce a useful theory (...) just by having a bright idea distantly related to what they imagine to be the facts. Even more unlikely is that they will produce a good theory at their first attempt. It is amateurs who have one big bright beautiful idea that they can never abandon. Professionals know that they have to produce theory after theory before they are likely to hit the jackpot. The very process of abandoning one theory for another gives them a degree of critical detachment that is almost essential if they are to succeed." (Francis Crick, 398).

Conclusion after 20 years

1. DNA is never synthesized de novo from building blocks, but always on the basis of another DNA template (semi-conservative replication)
2. DNA is always first transcribed into mRNA, STOP codons do not matter at transcription. RNA-polymerase is required for transcription. Also a transcription factor is required. Both are enzymes.
3. splicing machinery (spliceosome) is required which consists of ribonucleoproteins (enzymes)
4. translation requires ribosomes (translational apparatus) consisting of ribosomal proteins
5. translation requires transferRNA (tRNA) and aminoacyl-tRNA-synthetases, the latter are enzymes.

"It should be remembered that these proteins and RNAs of the primitive ribosomes (and other complex machineries) were not DNA coded. They were the random polymers of amino acids and nucleotides, chemically synthesized in the primordial pond. Rare associations of proteins and nucleic acids into "nucleoproteins" could carry out flashes of activities such as duplicating DNA (DNA replication), copying DNA into RNA (transcription), editing and splicing RNA (RNA splicing) and decoding RNA into protein (translation) in the primordial soup." page 210 (bold added) (418).

Appendix: Genetics Primer

Notes & References

1. Senapathy: "When I initially tried to explain my theory to my wife, I said, All the organisms could have come about just as they are, independently from the primordial pond. Her response..." (p.295). Please note, she forgot to ask about humans.
2. Source of chromosomes. These chromosomes are not from Senapathy's book. There are no chromosomes in his book. That is the point.
3. Only male honeybees hatch from unfertilized eggs [are haploid], but female honeybees hatch from fertilized eggs [are diploid], therefore that won't help independent origin theory very much. See: Olivia Judson(2002) Dr. Tatiana's sex advice to all creation, p.18 . Hermaphrodites (organism with both female and male sex organs) usually need another individual to reproduce.
4. Helen Pearson: Human genetics: "Dual identities", news feature, Nature 417, 10-11 (2002), 2 May 2002.
5. See for a full exposition for the non-specialist Mark Ridley (2000) Mendel's Demon. Gene Justice and the Complexity of Life (review), Chapter 6 "Darwinian merger and acquisition" is about the far reaching implications of having mitochondria in the cell.
6. Christian de Duve (2002) Life Evolving, Oxford Univeristy Press, p. 141.
7. Robert Pennock (2001) Intelligent Design Creationism and its Critics, p. 685.
8. S.G. Gregory et al (2002) A Physical map of the mouse genome. Nature AOP, published online 4 August 2002.
9. Carina Dennis and Richard Gallagher (2001), The Human Genome, p.120: "The largest apparently contiguous conserved segment in the human genome is on chromosome 4, including roughly 90,5 Mb of human DNA that is orthologous to mouse chromosome 5."
10. Similarities found in mouse genes and human's. Nicholas Wade, NewYork Times Science, 5 Dec 2002.
11. Comparision of Human chromosome 4 and Mouse chromosome 5.
12. Comparision of Human chromosome 17 and Mouse chromosome 11.
13. Comparision of Human chromosome 20 and Mouse chromosome 2.
14. A memorable misunderstanding on this site.
15. Evolution (Third Edition) on this site.
16. A Chemist's View of Life: Ultimate Reductionism & Dissent on this site.
17. Ernst Mayr (2001) What Evolution is, p.46. See also: Lynn Margulis(1998) Five Kingdoms. An illustrated guide to the phyla of life on earth, third edition. p.12.
18. Senapathy has a short paragraph What is a "seed cell"? (p.307), in which he uses 'haploid' and 'diploid', but there he neither explains what a seed cell is, nor how a diploid cell arises out of the primordial pond.
19. Portrait of a molecule by Philip Ball. This is a good article for those who think that a genome is just naked DNA. Nature 421, 421 - 422 (2003) (free). Have a look at the beautiful diagram of the 3-D structure of the chromosome showing that a genome is more than just the sequence of the bases! Looking at this image it is clear that Senapathy's discovery about split genes in random DNA is almost irrelevant. He did not explain the massive amounts of highly specialised proteins (histones), which form the complex 3-D structure of the eukaryotic chromosome.
20. Richard Dawkins used the now famous weasel computer experiment to demonstrate the difference between one-step and cumulative selection in The Blind Watchmaker, chapter 3. See also my Spetner review.
21. David Foster attributed this argument to Thomas Huxley (see review of Foster's book).
22. Senapathy states (p.222) that the occurrence of the uninterrupted text of Shakespeare is improbable.
23. Senapathy easily contradicts his own theory: "Thus it is possible for the prokaryotic genome to have been derived directly from contiguous genes in the open primordial pond". (p.238)
24. In fact, this question is wrong. There is no such a thing is "the human genome". Only female and male human genomes exist.
25. "the primordial pond could have been productive for a very long geological time" (p.345).
26. "indentifiying exon-intron borders is a notoriously difficult task", Antoine Danchin(2002) "The Delphic Boat", p.238.
27. Charles Spruck (2003) Requirement of Cks2 for the first metaphase/anaphase transition of mammalian meiosis. Science 300 (5619):647. 25 Apr 2003.
28. Whenever Senapthy is uncertain, he says "absolutely". The word occurs 138 times in his book!
29. Even Jesus, the son of God, had a mother. Significantly, this is claimed by people who otherwise accept miracles. However, Adam and Eve did not have a mother and father, but were created as adults. Senapthy's creatures also did not have a father and mother. The biblical creation story and Senapthy's scenario both are examples of independent origin. Even an orphan had a father and a mother.
30. A Conversation with James D. Watson, Scientific American, March/April 2003.
31. David Haig (2002) Genomic imprinting and kinship, Rutgers University Press, p.11. A further reason for the absence of parthenogenesis in animals is that the sperm also contributes the centrosome to the egg which is essential for initial divisions of the fertilized egg (Christiane Nüsslein-Volhard, 2006, p.15).
32. John Maynard Smith & Eörs Szathmáry (1999) The Origins of Life. From the Birth of Life to the Origin of Language. Furthermore, the members of higher levels are composed out of members of lower levels.
33. Graur and Li (2000) Fundamentals of Molecular Evolution. Second edition. p. 136.
34. Donald Forsdyke (2001) The Origin of Species Revisited, p. 103. (see review on this site).
35. Syozo Osawa (1995) Evolution of the Genetic Code, p. 45.
36. Michael Majerus (2003) Sex wars. - Genes, bacteria, and biased sex ratios, p.63,66.
37. Actually, meiosis is more complex. In males, the products of meiosis are four sperm, each sex chromosome in the original diploid cell being present in two of the products. In females of most species, however, only one egg is produced for each parent cell that undergoes meiosis, the other three haploid products together giving rise to the yolk of the ensuing egg. See also review of Mendel's Demon (Unexpected predictions and explanations).
38. Jan Sapp (2003) Genesis. The Evolution of Biology, Oxford University Press, paperback, p.x (Prefeace). This is elaborated in the chapter "Beyond the Genome".
39. M. Lynch (2002) 'Intron evolution as a population-genetic process' Proc. Natl. Acad. Sci. U.S.A. 99, 6118 (2002)
40. Paul Davies (1999) The Fifth Miracle. The Search for the Origin and Meaning of Life. p.119. Very important book!
41. What is known about the function of introns? , Scientific American, Ask the experts/Biology, 1999. Of course Senapathy could not have known this in 1994.
42. Louis Berman (2003) The Puzzle. Exploring the evolutionary puzzle of male homosexuality, p.478
43. Tibor Ganti (2003) The Principles of Life, Oxford University Press. (review). Furthermore, Ganti writes: "A living organism can never be developed from genetic material alone", "An egg, a seed, or a spore must always contain the substances of the cytoplasm". p.126.
44. Freeman Dyson (1999) "Origins of Life", second edition. p.18.
45. J.J. Emerson et al (2004) "Extensive Gene Traffic on the Mammalian X Chromosome", Science 303, nr 5657, 23 Jan 2004, pp. 537-540.
46. However, retrogenes are known for a long time. Examples of intronless retrogenes are: PGK (1987), calmodulin gene (1987), globin gene (1987), actin gene (1985). See Wen-Hsiung Li (1997), p.347.
47. S. J. Gould (2002) "The Structure of Evolutionary Theory", pp 252-253, 325, 527-528, 1174 (slightly adapted).
48. Solving the origin of life without the origin of species is difficult enough. However, even the origin of life itself is difficult enough because it commonly includes the origin of the genetic code. Hungarian chemist Gánti simplified the question by distinguishing between the origin of life an the origin of the genetic code.
49. Motomichi Matsuzaki et al (2004) 'Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D', Nature 428, 653-657. 08 Apr 2004. This species has 5331 genes, only 26 genes have introns.
50. Iris Fry (2000) The emergence of life on earth, p.56, 170.
51. Paul G. Falkowski and Colomban de Vargas (2004) Shotgun Sequencing in the Sea: A Blast from the Past? Science, 304, 58-60, 2 Apr 2004.
52. Iain Cheeseman and Arshad Desai (2004) Cell division: Feeling tense enough?, Nature, 428, 32-33, 4 March 2004.
53. Radu Popa (2004) "Between Necessity and Probability: Searching for the Definition and Origin of Life", p. 95-96. [ 18 June 2004 ]
54. David Bainbridge (2000) Making babies. The science of pregnancy, page 35-36.
55. Philip Ball (2004) "Synthetic Biology: starting from scratch", Nature, 431, 624-626 (7 Oct 2004). "Bacterial genomes are within the range of current DNA-synthesis technology" says John Mulligan, president of the DBA-synthesizing company Blue Heron Technology. But bacterial genomes must be embedded within a cell and its attendant biochemical machinery, making them much harder to synthesize than viruses.". [ 9 Oct 2004 ]
56. Why are stem-cells so important? Stem-cell biology is the second pillar of twenty-first-century biology. If a genome were enough, why are stemm cells so important for medicine? See: Ann Parson (2004) The Proteus Effect: Stem Cells and their Promise for Medicine. [ 24 Oct 2004 ]
57. Mark T. Ross et al (2005) "The DNA sequence of the human X chromosome.", Nature, 434, 17 Mar 2005, 325-337.
58. Christian de Duve (2002) Life Evolving, p.38.
59. Gil Ast (2005) The Alternative Genome, Scientific American March/April 2005 pp 40-47.
60. Douglas Futuyma (2005) Evolution, Sinauer Associates, page 53 and 440. (figures adapted for the web).
61. This is similar to explaining everything by saying 'God created the perfect fit between organism and environment'.
62. Large genomic differences explain our little quirks, Nature, 19 May 2005, 252.
63. Patrick Forterre (France) argues "that bacteria probably evolved more recently, and that LUCA was in fact a eukaryote", NewScientist 3 Sept 2005, p.28. (LUCA=Last Universal Common Ancestor). So Forterre seems to suggest that bacteria evolved from eukaryotes, but the difference with Senapathy is that Forterre does not claim that all eukaryotes arose independently. So although Forterre's view is highly unorthodox and implausible, Senapathy's view is a million times more unlikely.
64. Nick Lane (2005) Power, Sex, Suicide. Mitochondria and the Meaning of Life, p.143.
65. Asexual reproduction in animals is rare: the freshwater polyp Hydra reproduces by budding and some insects like aphids show life phases of quick multiplication through diploid eggs that form large, genetically identical clones. But in difficult times, even these animals reproduce sexually. (Christiane Nüsslein-Volhard, 2006, p.21).
66. Please note that the primordial pond illustration on the cover shows a turtle, a frog, a crab, a butterfly, a worm, a fern, but no mammal and no human being. Please note that the illustration suggest frogs develop directly from DNA, but in reality they develop from tadpoles. Similarly, butterflies develop from larva; pupa (not in water!).
67. Blowing In The Wind. Seeds & Fruits Dispersed By Wind. (a beautifully illustrated page about all kinds of seed dispersal).
68. Robert Shapiro (2007) 'A simpler Origin for Life', Scientific American, june 2007, page 28.
69. Alec Panchen (1993) Evolution, p.175.
70. Reduced fitness in individuals due to homozygous deleterious alleles is known as "inbreeding depression". See: Scott Freeman and Jon Herron (2007) 'Evolutionary Analysis', page 270. See also: "the analysis found more than 4 million variants between Venter's maternal and paternal chromosomes. This suggests that humans differ by 0.5%, not 0.1%, as suggested by earlier estimates." Jon Cohen (2007) Venter's Genome Sheds New Light on Human Variation, Science, 7 Sep 2007. On the other hand inbreeding (of dogs) can result in extremely long stretches of identical DNA common in different individuals of the same breed -millions of bases long compared to the typical tens of thousands of bases in humans. This is artificial selection with probably high costs (Science 21 September 2007). It is no accident that DNA of dog breeds are now investigated for genes for 18 diseases including four cancers, four inflammatory disorders, and three heart diseases.
71. Catherine Jessus & Olivier Haccard (2007) 'Fertilization: Calcium's double punch', Nature 449, 297-298 (20 September 2007).
72. David Beerling (2007) The Emerald Planet: How Plants Changed Earth's History, pp.180-183. There are regions on earth (Athi Plains in Kenya) were C₃ and C₄ plants coexist, so that would be the place for Senapathy's primordial pond!
73. See: Carl Woese (review).
74. Catherine Brady (2007) Elizabeth Blackburn and the Story of Telomeres: Deciphering the Ends of DNA, The MIT Press.
75. Erika Check Hayden (2008) 'Evolution: Scandal! Sex-starved and still surviving', Nature, 10 april 2008. " "Bdelloid rotifers reproduce entirely without males: females package a complete copy of their DNA into eggs that develop, sans fertilization, into the next generation. Asexual reproduction certainly isn't unheard of in the animal world: parasitic bacteria force some insects to reproduce without males and female sharks kept alone in captivity have surprised their keepers by giving birth to baby sharks."
76. Vaclav Smil Energy in Nature and Society, MIT Press: 2008. 512 pp. reviewed in Nature, 10 april 2008.
77. David A. Wheeler et al (2008) 'The complete genome of an individual by massively parallel DNA sequencing', Nature, 452, 872-876 (17 April 2008)
78. Elliott Sober (2008) Evidence and Evolution. The logic behind the science, p.116.
79. Erwan G. Roussel et al (2008) 'Extending the Sub-Sea-Floor Biosphere', Science, 23 May 2008.
80. For this amazing story see: Audubon Magazine. For a map see here. If the primordial pond is at sea level, do these geese survive at that level? How does the bizar migratory behavior originate? Random? That's a helpful explanation! Senapathy never tells us when, and where the primordial pond existed!
81. In fact when one looks closely to the quote from page 204, Senapathy is describing random mutation followed by natural selection!!!
82. See for explanation 'Vicious circle' box in my review of Hubert Yockey. This is a devastating obstacle for Independent Origin for the same reason that any mutation in the tRNA genes is lethal. See also: 'Does life look unlike evolution?' in my review of Walter Remine.
83. "RNA nucleotides have never been synthesized from scratch, in spite of decades of focused effort" (Robert M. Hazen (2005) Genesis. The scientific quest for life's origin, p.219. Also: "Nucleotides, the building blocks of DNA have never been produced in any prebiotic synthesis experiment" (Barton, p.95). Senapathy can never solve this problem by supposing that nucleotides where synthesised under genome control, because without nucleotides no genomes!
84. But not impossible. It is quite funny that Senapathy did not claim that with enough time prokaryote genomes could originate.
85. Gordon Campbell in: M.R. Wright (2000) 'Reason and necessity'.
86. Pier Luigi Luisi (2006) The Emergence of Life. From chemcial origins to synthetic biology, page 208.
87. Sheref S. Mansy et al (2008) 'Template-directed synthesis of a genetic polymer in a model protocell', Nature, 3 Jul 2008.
88. "Neo-Darwinism is in fact falsifiable, for there are many empirically testable claims made, for example within modern genetics which currently explains the core principle of inheritance. However, if it were to be falsified a new theory would have to replace it, in order to explain design in a non-theological fashion, and this would have very many features in common with neo-Darwinism simply because of the explanatory burden such a theory would have to carry." Thomas E. Dickins in: Evolutionary Psychology, 2005. 3: 79-84. This is very interesting: not only any alternative to evolution needs to explain the same set of facts, it also is expected to have much in common with neo-Darwinism. This is exactly what Senapathy is doing: he copies natural selection and common descent into his theory!!! What he does not do is use the same set of data as neo-Darwinism. Furthermore, Intelligent Design theorist Michael Behe incorporates natural selection and common descent into his ID theory!
89. Nicholas H. Barton, Derek E.G. Briggs, Jonathan A. Eisen, David B. Goldstein, Nipam H. Patel (2007) Evolution, Cold Spring Harbor Laboratory Press, hardback 833 pp. (my review).
90. See for the probability of the spontaneous origin of a well-designed body: Richard Dawkins (1991) The Blind Watchmaker, Penguin books 1991 paperback edition, page 146.
91. Additionally, meiotic recombination shuffles the genome, so each generation inherits a new combination of parental traits. How does Senapathy's theory explain the origin and continued existence of such a widespread, complex and costly proces as meiotic recombination? Meiotic recombination contradicts the idea that genomes are essentially fixed. What is the purpose of a recombination of parental genomes?
92. John Maynard Smith (1999) The Origin of Life, page 3.
93. John Maynard Smith (1995,1997) The Theory of Evolution, Cambridge University Press paperback. p.110.
94. I overlooked this figure and his claim that the primordial pond coincides with the Cambrian explosion. However, it only makes my argument stronger and clearer.
95. Senapathy appears to know that chromosomes occur in pairs. On pag 588 in note 109 he mentions homologous chromosomes. He even knows that one chromosome of a homologous pair of chromosomes is from the father, the other from the mother.
96. However, he seems to adopt an infinite universe of DNA sequences which does the trick for him.
97. Of the myriad problems of this scenario I mention a simple error: "Only those individuals with the absolutely right organs will survive" is not correct for reproductive organs! The situation is not analogous. One does not need sex organs to survive, while one does need hart, lungs, kidney, liver, mouth, teeth, stomach, intestines, and anus to survive. Infertile people don't die. See: 'The female and male genome' on this page.
98. A good overview is: chapter 17 in: Stephen Stearns and Rolf Hoekstra (2005), second edition.
99. page 8. This is a revealing and charming description of his naive way of thinking.
100. Daniel Fairbanks (2007) Relics of Eden. The powerful evidence of evolution in human DNA, p.154.
101. John Allman (2000) Evolving Brains, Scientific American Library, page 86
102. Dylan Chivian et al (2008) 'Environmental Genomics Reveals a Single-Species Ecosystem Deep Within Earth', Science 10 October 2008.
103. Science Daily (2003) Ultra-low Oxygen Could Have Triggered Die-offs, Spurred Bird Breathing System, Oct. 31, 2003.
104. Helen Pearson (2008) 'Outcry at scale of inheritance project', Nature, 10 October 2008
105. Periannan Senapathy et al (2008) 'Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences', Plos One, October 20, 2008. Open Access.
106. When did this processing occur? Some evidence suggests that Senapathy means prebiotic processing, because he writes: "Stop codons occurred too frequently to allow functional proteins to be encoded in random DNA" (my emphasis). Life could not have started with too short genes and proteins, that would be incompatible with life. Life requires functional proteins. On the other hand, Senapathy also provides evidence that a substantial amount of processing occurred after the origin of random DNA: "The average exon length from the intron-rich genomes is about 170 bases whereas that expected from random ORF lengths is 60 bases. This may indicate that there has been a selection for longer exons within the allowed maximum ORF length of 600 bases for optimizing the frequency of suitable exon lengths." (my emphasis). Further evidence supports this interpretation: "mRNA splicing evolved to overcome the problem of the frequent occurrence of stop codons in primordial random DNA"; "RNA splicing evolved to circumvent the problem of short ORFs"; "According to the ROSG model, mRNA splicing evolved to overcome the problem of the frequent occurrence of stop codons in primordial random DNA that severely restricted ORF lengths." This is vague. Senapathy is not clear about it. A good scientific theory should be clear.
107. Computational Discovery of Internal Micro-Exons
108. Stewart Scherer (2008) A Short Guide to the Human Genome, p.32.
109. Ann Gibbons (2008) 'The Birth of Childhood', Science 14 November 2008.
110. Henry Nicholls (2008) 'Darwin 200: Let's make a mammoth', Nature 456, 310-314 (2008). Let's make a mammoth from its DNA is a perfect analogy with Senapathy's project to create an animal from its genome! All the problems and obstacles to create a mammoth from its DNA appear in Senapathy's scenario!
111. updated 13 Mar 2013. It is chemically possible to have 6 bases (3 base pairs), 8 bases (4 base pairs), 12 bases (6 base pairs) (Nicholas Barton et al (2007) Evolution, page 561) or maybe even 20 bases (10 pairs). In that case each base codes for one amino acid and the length of DNA would be reduced to a third of the original length. Shorter DNA molecules would be more efficient: it costs less energy and less building blocks to synthetize and replicate. However, the difficulty would be to find bases that are able to form pairs with a constant diameter to enable a stable, regular double helix structure. The disadvantage would be that 20 different bases must be synthesized, coded for and maintained.
     On the other hand, organisms could do with only CG pairs or only AT pairs. Information in DNA can still be coded with one base pair. Each strand would have a sequence such as GCCGGGGC..., and each amino acid could be coded by four or five bases instead of three. Replication with only one base pair would be most accurate because only G or C (say) would need to be distinguished. The disadvantage would be that the length of DNA to encode proteins would much longer, almost double. Example of using the four-base codon CGGG in a cell-free translation system: FRET analysis of protein conformational change through position-specific incorporation of fluorescent amino acids.
112. In an interview Jerry Coyne says: "I don't know of any challenge to evolution that's ever come from a non-religious person. Personally I've never experienced one.". Senapathy is such a non-religious critic of evolution.
113. Noncoding DNA
114. Actually Carl Woese showed that 'Prokaryotes' must be replaced with 'Archaea' and 'Bacteria' or alternatively with 'microorganisms'. See also: Norman R. Pace (2009) 'It's time retire the prokaryote', Microbiology Today, May 2009, 85-87.
115. Kurland CG, Collins LJ, Penny D (2006) Science 312:1011-1014. Quoted by Lynch
116. John S. Mattick and Igor V. Makunin (2006) 'Non-coding RNA', Human Molecular Genetics 2006 15.
117. Eugene V. Koonin (2009) Darwinian evolution in the light of genomics, Nucleic Acids Research, 2009, Vol. 37, No. 4 1011-1034. free full text.
118. Henrik Kaessmann (2009) More Than Just a Copy, Science.
119. Carol Greider, Elizabeth Blackburn and Jack Szostak received the Nobel prize 2009 for their work on telemeres. Nature
120. Fuyuki Ishikawa and Taku Naito (1999) 'Why do we have linear chromosomes? A matter of Adam and Eve', Mutation Research/DNA Repair Volume 434, Issue 2, 23 June 1999, Pages 99-107: "Bacterial circular chromosomes have sporadically become linearised during prokaryote evolution".
121. Dirk Schübeler (2009) 'Epigenomics: Methylation matters' Nature 462, 296-297 (19 November 2009)
122. Dennis McCarthy (2009) Here be dragons. How the study of animal and plants distributions revolutionzied our views of life and Earth, p.100.
123. Dennis McCarthy (2009) 'Here be dragons', p.186 and 191.
124. See also: "As Simpson himself pointed out, -any event that is not absolutely impossible ... becomes probable if enough time elapses" (Nature, 4 Feb 2010) about Madagascar species. What we need is quantification.
125. Stewart Scherer (2008) A Short Guide to the Human Genome, p.41.
126. Explanation of basic principles: Reading the Genetic Code (Nature Education).
127. Michael Yarus (2010) Life from an RNA world, Harvard University Press.
128. This very profound objection to independent origin occured to me only 7 years after I started this review.
129. Elizabeth Pennisi (2010) 'Synthetic Genome Brings New Life to Bacterium', Science, 21 May 2010.
130. Douglas L. Theobald (2010) 'A formal test of the theory of universal common ancestry', Nature 465 219-222 (13 May 2010). But see: The common ancestry of life.
131. Nick Lane & William Martin (2010) 'The energetics of genome complexity', Nature, 467 929-934 21 October 2010
132. France Denoeud (2010) 'Plasticity of Animal Genome Architecture Unmasked by Rapid Evolution of a Pelagic Tunicate', Science, Published Online 18 November 2010.
133. Felisa A. Smith et al (2010) 'The Evolution of Maximum Body Size of Terrestrial Mammals', Science, 26 November 2010.
134. Elizabeth Pennisi (2010) Shining a Light on the Genome's 'Dark Matter', Science 17 dec 2010
135. 'meaningless/meaningful': is relative to the language. This also holds for the genetic code language! Senapathy would have found genes from an arbitrary genetic language in a random piece of computer DNA, because meaningful genes can be produced by any genetic language. The point is however, that in a computer experiment it's easy to use the same language during the experiment, while in natural experiments there is nothing that ensures the same genetic language during the production of even one genome, let alone all genomes.
136. O.B. Ptitsyn (1984) 'Random sequences and protein folding', Journal of Molecular Structure: THEOCHEM Volume 24, Issues 1-2, July 1985
137. V. S. Pande et al (1994) 'Nonrandomness in protein sequences: Evidence for a physically driven stage of evolution?' PNAS Vol. 91, pp. 12972-12975, December 1994.
138. Anthony D. Keefe & Jack W. Szostak (2001) 'Functional proteins from a random-sequence library', Nature 410, 715-718.
139. Codon usage in E. coli and: codon usage.
140. D M Raup and J W Valentine Multiple origins of life PNAS May 1, 1983 vol. 80 no. 10 2981-2984
141. Senapthy uploaded 3 papers to Nature Precedings (Documents on Nature Precedings are not peer-reviewed, but any visitor can comment):
     - Origin of biological information: Inherent occurrence of intron-rich split genes, coding for complex extant proteins, within pre-biotic random genetic sequences 13 December 2010 07:04
     - The inherent occurrence of complex intron-rich spliceosomal split genes, including regulatory and splicing elements, within pre-biotic random genetic sequences 13 December 2010 07:27
     - Parallel genome assembly from pre-biotic split-genes: A solution for the mosaic genome conundrum 13 December 2010 07:53
     I submitted 3 comments to the first document, but only one was posted. Remarkably, that comments are blocked while simultaneous submitting 3 large articles is no problem at all! Only later the second one appeared. And on 28 February 2011 Senapathy replied.
142. T. Mourier and D. C. Jeffares (2003) 'Eukaryotic Intron Loss', Science p.1393, 30 May 2003.
143. Sakharkar KR (2006) 'Functional and evolutionary analyses on expressed intronless genes in the mouse genome', FEBS Lett. 2006 Feb 20;580(5):1472-8. Epub 2006 Jan 31.
144. Jain M et al (2008) 'Genome-wide analysis of intronless genes in rice and Arabidopsis', Funct Integr Genomics. 2008 Feb;8(1):69-78. Epub 2007 Jun 20.
145. Syozo Osawa (1995) Evolution of the Genetic Code, Oxford University Press. page 150.
146. Dmitry V. Fyodorov & James T. Kadonaga (2002) 'Dynamics of ATP-dependent chromatin assembly by ACF', Nature 418, 896-900 (22 August 2002)
147. C. G. Kurland, L. J. Collins, D. Penny (2006) Genomics and the Irreducible Nature of Eukaryote Cells, Science 19 May 2006
148. T. M. Embley, W. Martin (2006) 'Eukaryotic evolution, changes and challenges', Nature 440, 623 (Mar 30, 2006):
     "In recent years, even that has been called into question, as some phylogenies have suggested that prokaryotes might be derived from eukaryotes".
149. Eugene V. Koonin (2009) 'Intron-Dominated Genomes of Early Ancestors of Eukaryotes', J Hered (2009) 100 (5): 618-623.
150. N. H. Barton et al (2007) Evolution, Cold Spring Harbor Laboratory Press, p.220.
151. Group I catalytic intron in wikipedia. Homing endonuclease recognition sequences are long enough to occur randomly only with a very low probability: approximately once every 7×10¹⁰ bp.
152. Scott William Roy, Walter Gilbert (2006) The evolution of spliceosomal introns: patterns, puzzles and progress, Nature Reviews Genetics Volume 7 March 2006 211
153. Francisco Rodríguez-Trelles, Rosa Tarrío, Francisco J. Ayala (2006) 'Origins and Evolution of Spliceosomal Introns', Annu. Rev. Genet. 2006. 40:47-76. Very imporant article (introns-first hypothesis).
154. Sequence and organization of the human mitochondrial genome, Nature (1981) 290: 457-65. Also: The mouse mitochondrial genome displays exceptional economy of organization, protein-coding genes with zero or few noncoding nucleotides between coding sequences .
155. Lawrence A. David, Eric J. Alm (2011) 'Rapid evolutionary innovation during an Archaean genetic expansion', Nature, 469, 93-96. 06 January 2011
156. GenScript (accessed 6 Jan 2011)
157. "Our findings thus show that any split gene that can encode complex proteins which form the structure of the spliceosome or any other eukaryotic cellular organelle," (p.8). This equals to the claim that organelles were designed.
158. Brian Hall, Benedikt Hallgrimsson (2008) Strickberger's Evolution, Fourth edition, page 139.
159. Lee R. Kump (2010) 'Earth's Second Wind', Science 10 December 2010
160. Radu Popa (2004) Between Necessity and Probability: Searching for the Definition and Origin of Life, Springer, p. 67-68.
161. In previous versions I stated only that every OOL theory needs to explain the restricted choice of the genetic code in the face of the huge freedom of choice, but later I realised that precisely this freedom of choice forces any theory of independent origin to predict a huge diversity of genetic codes (11 Jan 11).
162. "The non-universal genetic codes are not produced randomly, but are derived from the universal genetic code as the result of a series of non-disruptive changes" (Syozo Osawa (1995) 'Evolution of the Genetic Code', p.171). Senapathy's theory would predict that non-universal codes are (1) random, (2) ubiquitous, (3) originated in the beginning. All predictions are wrong.
163. Michael Lynch (2002) 'Intron evolution as a population-genetic process', Proc Natl Acad Sci U S A. 2002 April 30.
164. Michael Lynch, John S. Conery (2003) 'The Origins of Genome Complexity', Science 302 21 Nov 2003.
165. Eugene V Koonin (2006) 'The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate?', Biology Direct. Koonin seems to be a little bit genome-centered too! (with response from Ford Doolittle).
166. D. Fridmanis et al (2007) 'Formation of new genes explains lower intron density in mammalian Rhodopsin G protein-coupled receptors', Mol Phylogenet Evol. 2007 Jun; 43(3):864-80.
167. Tom Strachan, Andrew Read (2000) Human Molecular Genetics Second Edition, p.150-152.
168. Sarah Blaffer Hrdy (2009) Mothers and Others, p. 101.
169. JE Darnell, Jr (1978) Implications of RNA-RNA splicing in evolution of eukaryotic cells, Science 22 December 1978:
     Abstract: "The differences in the biochemistry of messenger RNA formation in eukaryotes compared to prokaryotes are so profound as to suggest that sequential prokaryotic to eukaryotic cell evolution seems unlikely. The recently discovered noncontiguous sequences in eukaryotic DNA that encode messenger RNA may reflect an ancient, rather than a new, distribution of information in DNA and that eukaryotes evolved independently of prokaryotes."
     
170. Martin and Koonin (2006) Introns and the origin of nucleus-cytosol compartmentalization, Nature 440, 41-45 (2 March 2006)
171. Daniel C. Jeffares, Tobias Mourier, David Penny (2006) 'The biology of intron gain and loss', TRENDS in Genetics Vol.22 No.1 January 2006
172. In theory Senapathy could argue that prokaryotes originated independently and had as many introns as eukaryotes but lost them completely, since several publications argue that clear instances of massive intron loss make the case for complete intron loss in prokaryotes plausible. This implies strong Darwinian selection.
173. Anthony Poole, Daniel Jeffares, David Penny (1999) Early evolution: prokaryotes, the new kids on the block, BioEssays 21:880-889, 1999.
174. Morgan Ryan (2011) Unauthorized reproduction not prohibited, American Scientist, Vol 99, p. 30.
175. M.B. Shapiro, P. Senapathy (1987) "RNA splice junctions of different classes of eukaryotes" is cited in: László Patthy (1999) Protein Evolution, p. 148.
176. Monya Baker (2011) 'Genomics: Genomes in three dimensions', Nature, 470, 289-294 (10 February 2011)
177. Tom Misteli (2007) Beyond the Sequence: Cellular Organization of Genome Function, Cell 128, 787-800, February 23, 2007
178. Tom Misteli (2011) The Inner Life of the Genome Scientific American Feb 2011.
179. Dan Graur, W H Li (2000) Fundamentals of Molecular Evolution, p.289 and 296.
180. Guy M. Narbonne (2011) Evolutionary biology: When life got big, Nature 470, 17 February 2011
181. Eddo Kim (2007) Different levels of alternative splicing among eukaryotes, Nucleic Acids Res. 2007 January; 35(1): 125-131.
182. Aubrey E. Hill, Eric J. Sorscher (2006) The non-random distribution of intronless human genes across molecular function categories, FEBS Letters.
183. Ribozymes.
184. Francis Crick (1981) Life Itself. It's Origin and Nature, Simon and Schuster.
185. Monroe Strickberger (2000) Evolution, Third edition, p.143.
186. Michael IP (2005) Intron retention: a common splicing event within the human kallikrein gene family. Clin Chem. 2005 Mar;51(3):506-15.
187. Gene Splicing Overview & Techniques.
188. Andreas Wagner (2005) Energy Constraints on the Evolution of Gene Expression, Molecular Biology and Evolution, 22, 6 Pp. 1365-1374
189. Ner-Gaon H (2004) Intron retention is a major phenomenon in alternative splicing in Arabidopsis, Plant J. 2004 Sep;39(6):877-85.
190. Knowles DG, 2. McLysaght A (2009) Recent de novo origin of human protein-coding genes. Genome Research
191. Maren Krull, Jürgen Brosius and Jürgen Schmitz (2005) Alu-SINE Exonization: En Route to Protein-Coding Function, Molecular Biology and Evolution 22, 8 1702-1711
192. Manfred Eigen (1992) Steps towards Life. A perspective on Evolution, Oxford University Press. (paperback edition: 1996) See also wikipedia article Error threshold.
193. Richard Dawkins (1986) The Blind Watchmaker, chapter 3.
194. P Senapathy (1986) Origin of eukaryotic introns: a hypothesis, based on codon distribution statistics in genes, and its implications, PNAS April 1, 1986 vol. 83 no. 7 2133-2137. The abstract is a beautiful succinct summary (written 8 years before his book) of his whole theory!
195. Francesco Catania, Xiang Gao and Douglas G. Scofield Endogenous Mechanisms for the Origins of Spliceosomal Introns, J Hered (2009) 100 (5): 591-596. Quote: "Spliceosomal introns have also been suggested to directly arise from random primordial and canonical ancestral gene sequences (the 'split-gene model' and the 'proto-splice site model', respectively). In particular, Senapathy (1986)". Further Senapathy (1986) is quoted in: Masaru Tomita et al (1996) 'Introns and Reading Frames: Correlation Between Splicing Sites and Their Codon Positions', Mol. Biol. Evol. 13(9):1219-1223.
196. Lewin's GENES X, 2011, p. 86.
197. Donald R. Forsdyke & James R. Mortimer (2000) Chargaff's legacy, Gene (2000) 261, 127-137
198. Cory Y. McLean et al (2011) Human-specific loss of regulatory DNA and the evolution of human-specific traits, Nature 10 Mar 2011
199. Manyuan Long and Carl Rosenberg (2000) Testing the 'Proto-splice Sites' Model of Intron Origin: Evidence from Analysis of Intron Phase Correlations, Mol Biol Evol (2000) 17 (12): 1789-1796. Another way of measuring intron phases is expressing exon length as multiples of 3, 3N+1, 3N+2.
200. Compare with W F Doolittle: 'Genes in pieces: Were they ever together?' Nature 1978, 272:581-582.
201. Jeffrey M. Perkel (2011) Synthetic Genomes: Building a better Bacterium, Science, 25 Mar 2011
202. See my review of Information theory and molecular biology by Hubert Yockey.
203. Eileen E. M. Furlong (2011) Molecular biology: A fly in the face of genomics, Nature 471, 458-459 24 March 2011
204. S Ragsdale (2011) Biochemistry: How two amino acids become one, Nature, 31 Mar 2011 shows that the stopcodon UAG from methanogenic Archaea encodes the new amino acid Pyrrolysine. So it only has two stop codons. Tetrahymena species recognize only UGA as a stop codon, while Euplotes species recognize only UAA and UAG as stop codons (Joe Salas-Marco et al, 2006).
205. Ryan E. Mills et all (2011) 'Natural genetic variation caused by small insertions and deletions in the human genome', Genome Research April 1, 2011
206. Gretchen Vogel (2011) 'Do Jumping Genes Spawn Diversity?, Science, 15 April 2011.
207. Jevon Plunkett et al (2011) An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing, PLoS Genetics April 2011
208. Kevin Plaxco and Michael Gross (2006) Astrobiology. A Brief Introduction, page 71: "These amino acids were almost certainly introduced by biochemistry after the origins of life".
209. Hadas Keren, Galit Lev-Maor & Gil Ast (2010) Alternative splicing and evolution: diversification, exon definition and function, Nature Review Genetics, 11, 345-355 (May 2010)
210. Elizabeth Pennisi (2011) 'Green Genomes', Science 17 Jun 2011
211. "It is worth noting that the average length of metazoan exons (125 - 165 bp) is similar to the length of DNA that wraps around a nucleosome (147 bp), which suggests that nucleosome occupancy might confer purifying selection on exon length. However, the length of an average human exon is only 126 bp." From ref 209.
212. Elçin Ünal et all (2011) Gametogenesis Eliminates Age-Induced Cellular Damage and Resets Life Span in Yeast, Science, 24 Jun 2011.
213. "The oceans are teeming with viruses — typically, there are 100 billion viral particles per litre of water in the top 50 metres of most marine ecosystems. With an average of ten viruses for each bacterial cell, these parasites impose a tight control over the composition of marine microbial communities. The 'arms race' hypothesis holds that the selective pressure exerted by viruses continuously triggers adaptive mutations in the bacterial genomes, with counteracting genetic adaptations occurring at a similar pace in the parasites." Science 30 jun 2011.
214. Mingyao Li et al (2011) Widespread RNA and DNA Sequence Differences in the Human Transcriptome, Science, 1 Jul 2011 :"We have uncovered thousands of exonic sites where the RNA sequences do not match those of the DNA sequences, including transitions [changes a purine nucleotide to another purine] and transversions [substitution of a purine for a pyrimidine or vice versa]".
215. David Deamer (2011) First Life. Discovering the Connections between Stars, cells, and How Life Began. University of California Press, p. 183.
216. Denis Noble (2006) The Music of Life. Biology Beyond the Genome, Oxford University Press. See my short description on the Introduction page. The first four chapters are the most important, they explain what is wrong with genetic determinism.
217. See: David Deamer (note 215) page 214: "Can genetic information really appear out of nowhere, by chance?" where he reports the experiments of Bartel and Szostak (1993) "Isolation of new ribozymes from a large pool of random sequences', who began by synthetizing many trillions of different random RNA molecules 300 nucleotides long and found RNAs with catalytic activity. Furthermore, selection and amplification are involved, which are absent from Senapathy's scenario. Deamer concludes "The inescapable conclusion is that genetic information can appear out of random mixtures, as long as there are populations containing large numbers of polymeric molecules with variable sequences of monomers and a way to select and amplify specific property" (p.216). The conditions in this claim are extremely important! The problem here is: how do you get long polymeres in the first place? Long enough to be of catalytic value?
218. Warm and Cold-Blooded
219. The Central Dogma of molecular biology certainly reinforces genetic determinism because the direction of the flow of information is from DNA to RNA to proteins. This strongly suggests DNA is in control and there is no feedback.
220. Which came first, the bird or the smaller genome? 30 August 2007
221. Craig B. Lowe et al (2011) Three Periods of Regulatory Innovation During Vertebrate Evolution, Science, 19 August 2011.
222. A story of chromosome number, Nature 477, 9 1 September 2011
223. Y. Jiao et al (2011) Ancestral polyploidy in seed plants and angiosperms. Nature 473, 97 (2011).
224. T. E. Wood et al (2009) The frequency of polyploid speciation in vascular plants. Proc. Natl. Acad. Sci. U.S.A. 106, 13875 (2009).
225. Steven A. Frank (2009) Somatic evolutionary genomics: Mutations during development cause highly variable genetic mosaicism with risk of cancer and neurodegeneration, PNAS January 26, 2010 vol. 107
226. Centrosome (24 Sep 2011)
227. Kyle Vogan (2011) Maternal imprinting defect, Nature Genetics 43, 928
228. James Darnell (2011) RNA. Life's Indispensable molecule, p. 243.
229. Senapathy knows about the existence of the spliceosome in the Genetics Primer (p. 547, 555), although it does not occur in the index.
230. Evolution of nested gene arrangements, the ruvinsky lab.
231. Chun-Long Chen et al (2008) Genomewide Analysis of Box C/D and Box H/ACA snoRNAs in Chlamydomonas reinhardtii Reveals an Extensive Organization Into Intronic Gene Clusters, Genetics May 2008 vol. 179 no. 1 21-30.
232. Michael B. Clark et al (2011) The Reality of Pervasive Transcription PLoS Biology July 2011.
233. Eugene V Koonin, Tatiana G Senkevich, Valerian V Dolja (2006) 'The ancient Virus World and evolution of cells', Biology Direct 2006, 1:29. The authors use the words: "the primordial pool of primitive genetic elements"; "the primordial genetic pool", "The primordial gene pool", and "existence of a complex, precellular, compartmentalized but extensively mixing and recombining pool of genes"; "viral origin from the primordial genetic pool". However, "In this pool, RNA viruses would evolve first, followed by retroid elements, and DNA viruses.". So that is different from Senapathy: he starts with complete eukaryotic genomes. (I need to investigate this important publication! It seems that the authors make the mistake of 'protein-coding genes' without transcription and translation machinery!)
234. Stephen J. Freeland, et all (1999) Early Fixation of an Optimal Genetic Code, Mol Biol Evol (2000) 17 (4): 511-518.
235. A. D. Ellington (2009) Evolutionary origins and directed evolution of RNA, Int J Biochem Cell Biol. 2009 Feb;41(2):254-65. (See also Stuart A. Kauffman about random DNA libraries)
236. "A long explanation for introns", New Scientist, June 26, 1986 (see google books); "Exon, introns, and evolution", New Scientist, March 31, 1988 (see google books).
237. Martin Ackermann, Lin Chao (2006) DNA Sequences Shaped by Selection for Stability, PLoS Genetics, February 2006.
238. Woese, C. R. On the evolution of the genetic code. Proc. Natl Acad. Sci. USA 54, 1546–1552 (1965).
239. Tobias Warnecke, Laurence D. Hurst (2011) Error prevention and mitigation as forces in the evolution of genes and genomes, Nature Reviews Genetics 12, 875-881 (December 2011)
240. Brian P. Cusack, Peter F. Arndt, Laurent Duret, Hugues Roest Crollius (2011) Preventing Dangerous Nonsense: Selection for Robustness to Transcriptional Error in Human Genes, PLoS Genetics October 2011
241. Miodrag Grbic et al (2011) The genome of Tetranychus urticae reveals herbivorous pest adaptations, Nature 479, 487–492 (24 November 2011) Supplementary information Figure S2.4.2.
242. Richard Cordaux, Mark A. Batze (2009) The impact of retrotransposons on human genome evolution, Nature Reviews Genetics 10, 691-703 (October 2009) is a very usefull overview.
243. Erez Lieberman Aiden (2011) Zoom! Science 2 December 2011
244. William A. Wells (2005) There's DNA in those organelles, The Journal of Cell Biology, March 14 2005
245. Hans Ris and Walter Plaut (1962) Ultrastructure Of DNA-Containing Areas In The Chloroplast Of Chlamydomonas, The Journal of Cell Biology, 1 Jun 1962.
246. Eugene V. Koonin (2011) The Logic of Chance. Pearson Education, hardback.
247. Kevin N. Laland, Kim Sterelny, John Odling-Smee, William Hoppitt, Tobias Uller (2011) 'Cause and Effect in Biology Revisited: Is Mayr's Proximate-Ultimate Dichotomy Still Useful?', Science 16 Dec 2011.
248. RM Schwartz and MO Dayhoff (1978) 'Origins of prokaryotes, eukaryotes, mitochondria, and chloroplasts', Science 27 January 1978: 395-403.
249. Structure of the Mitochondrial Genome, Genetic Origins website.
250. "Translation in Escherichia requires the coordinated and complex interactions of at least 100 gene products." from: Ravi Jain, Maria C. Rivera, and James A. Lake (1999) Horizontal gene transfer among genomes: The complexity hypothesis, Proc. Natl. Acad. Sci. USA Vol. 96, pp. 3801–3806, March 1999
251. Stuart A. Kauffman (2011) Approaches to the Origin of Life on Earth, Life 2011, 1, 34-48 (Open Access)
252. Joan A. Steitz (2012) RNA Rejoice! Review of RNA Life's Indispensable Molecule by James Darnell, Science 6 January 2012
253. Ming Zou, Baocheng Guo, Shunping He (2011) 'The Roles and Evolutionary Patterns of Intronless Genes in Deuterostomes', Comparative and Functional Genomics, Volume 2011.
254. Brian K. Hall, Benedict Hallgrimsson (2008) Strickberger's Evolution Fourth Edition, p. 134.
255. Dennis W. Grogan (2002) Hyperthermophiles and the problem of DNA instability, Molecular Microbiology.
256. Scott Freeman and Jon Herron (2007) 'Evolutionary Analysis', page 657.
257. Martin Egli (2006) Uncovering DNA's 'sweet' secret. One particular curiosity: how did DNA and RNA come to incorporate five-carbon sugars into their "backbone" when six-carbon sugars, like glucose, may have been more common?
258. Miklos Csuros, Igor B. Rogozin, Eugene V. Koonin (2011) A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes, PLoS Computational Biology September 2011.
259. Igor B. Rogozin, Yuri I. Wolf, Alexander V. Sorokin, Boris G. Mirkin, and Eugene V. Koonin, (2003) Remarkable Interkingdom Conservation of Intron Positions and Massive, Lineage-Specific Intron Loss and Gain in Eukaryotic Evolution, Current Biology, Vol. 13, 1512–1517, September 2, 2003.
260. NCBI The RNA World and the Origins of Life.
261. Lindberg J, Lundeberg J. (2009) The plasticity of the mammalian transcriptome, Genomics 2010 Jan;95(1):1-6.
262. Furthermore, E. Koonin notes that the emergence of spurious (weak) transcription initiation sites in random DNA sequences is relatively easy (given the existence of Transcription factors of course) (p. 240, Note 246).
263. Aaron E. Engelhart and Nicholas V. Hud (2010) Primitive Genetic Polymers, Cold Spring Harbor Perspectives in Biology, 12 May 2010.
264. Aaron Klug (2004) 'The Discovery of the DNA Double Helix', Journal of Molecular Biology, Volume 335, Issue 1, 2 January 2004, Pages 3-26 (available as: klug-DNA.pdf)
265. The standard laboratory technique to isolate DNA includes digestion with proteinase which removes all proteins (histones).
266. How Many People Have Ever Lived On Earth? Population reference Bureau, assessed 9 Feb 2012.
267. Monya Baker (2012) Functional genomics: The changes that count, Nature 482, 257–262 09 February 2012
268. Kerstin Lindblad-Toh et al (2011) A high-resolution map of human evolutionary constraint using 29 mammals, Nature 478, 476–482 (27 October 2011)
269. Jurka J, et al (2007) Repetitive sequences in complex genomes: structure and evolution, Annu Rev Genomics Hum Genet. 2007;8:241-59.
270. Christian de Duve (2005,2006) Singularities. Landmarks on the Pathways of Life, p.81.
271. Eric S. Lander (2011) Initial impact of the sequencing of the human genome, Nature, 470, 187–197 (10 February 2011)
272. James Collins (2012) Synthetic Biology: Bits and pieces come to life, Nature 483, S8–S10 (01 March 2012)
273. Gregory P. Wilson, et al (2012) Adaptive radiation of multituberculate mammals before the extinction of dinosaurs, Nature 483, 457–460 (22 March 2012)
274. Tom Strachan, Andrew Read (2011) Human Molecular Genetics. Fourth Edition, on p. 274 is a table with 7 examples. (Info).
275. In theory, a protein or enzyme could originate spontaneously from amino acids. However, non-essential amino gacids, such as Glycine, must be synthesized from precursors (in this case from Serine) by enzymes (in this case by serine hydroxymethyltransferase, SHMT). Even if all amino acids were present, the precise order of the amino acids would be too unlikely to originate by chance. One needs genes for that.
276. Pregnancy: Why Mother's Immune System Does Not Reject Developing Fetus as Foreign Tissue, Sciencedaily, 7 Jun 2012.
277. Chris Todd Hittinger (2012): "As plants invaded land, lignin provided the rigidity necessary for vascular plants to grow above their rivals and move water and nutrients over long distances. Lignin is a dizzying web of polymerized phenylalanine derivatives with dozens of combinations of modifications and cross-links that make wood structurally sound ", Science 29 June 2012
278. Kenneth A. Johnson (2012) 'Biochemistry: DNA replication caught in the act', Nature 487, 177–178 (12 July 2012)
279. Anne-Ruxandra Carvunis et al (2012) Proto-genes and de novo gene birth, Natue 19 Jul 2012.
280. Dong-Dong Wu et al (2011) De Novo Origin of Human Protein-Coding Genes, PLOS Genetics, November 10, 2011. "Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee, supported by both transcriptional and proteomic evidence."
281. William A. Shear (2012) Palaeontology: An insect to fill the gap, Nature, 488, 34–35 (02 August 2012)
282. Mark Isalan (2012) Systems biology: A cell in a computer, Nature, 2 Aug 2012
283. Christof Koch (2012) Modular Biological Complexity, Science 3 August 2012. Koch discusses the complexity of living systems which are characterized by large numbers of highly heterogeneous components, be they genes, proteins, or cells. He applies his analysis to the human brain, but it can equally applied to the origin of an eukaryotic organism.
284. Alla Katsnelson (2010) Epigenome effort makes its mark, Nature 467, 646 (2010) 6 October 2010
285. Amy Maxmen (2012) Cancer research: Open ambition, Nature News feature 8 August 2012. (a story about cancer drug discoverer Jay Bradner). "Such control systems generally involve three types of protein: 'writers', 'readers' and 'erasers'. Writers attach chemical marks, such as methyl groups (to DNA) or acetyl groups (to the histone proteins that DNA wraps around); readers bind to these marks and influence gene expression; erasers remove the marks".
286. Kai Kupferschmidt (2012) Attack of the Clones, Science 10 August 2012: "Fungi have long been seen as the least interesting pathogens, but two catastrophes in the animal world have changed that view." "In just the past 5 years, scientists have discovered fungi affecting rattlesnakes, land crabs, avocado trees, cultured abalone, and the eggs of sea turtles".
287. The ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome, Nature 489, 57–74 (06 September 2012): "These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions.". One of the more remarkable findings is that 80% of the genome contains elements linked to biochemical functions, dispatching the widely held view that the human genome is mostly 'junk DNA' (Genomics: ENCODE explained). "Comparative genomic studies suggest that 3–8% of bases are under purifying (negative) selection and therefore may be functional". 13 Jun 2023: Warning: 80% soon appeared to be totally wrong! See Note 401.
288. Elizabeth Pennisi (2012) 'ENCODE Project Writes Eulogy for Junk DNA', Science 7 September 2012: "the Encyclopedia of DNA Elements (ENCODE), has found that 80% of the human genome serves some purpose". "The latest protein-coding gene count is 20,687, with hints of about 50 more, the consortium reports in Nature. Those genes account for about 3% of the human genome [including introns], less if one counts only their coding regions. So, if introns are excluded the percentage of DNA consisting of genes probably is about 0.3% of the total DNA in the human genome. "As a result of ENCODE, Gingeras and others argue that the fundamental unit of the genome and the basic unit of heredity should be the transcript–the piece of RNA decoded from DNA–and not the gene". 13 Jun 2023: Warning: 80% soon appeared to be totally wrong! Note 401.
289. Laurence Moran 'The Random Genome Project' and the original source is: Sean Eddy (8 Sep 2012): "The experiment that I'd like to see is the Random Genome Project. Synthesize a hundred million base chromosome of entirely random DNA, and do an ENCODE project on that DNA. Place your bets: will it be transcribed? bound by DNA-binding proteins? chromatin marked? Of course it will." Sunday, September 09, 2012. Addition: a random sequence may bind a transcription-factor, but that may not result in transcription.
290. The ENCODE Project Consortium An integrated encyclopedia of DNA elements in the human genome, Nature 489, 06 September 2012. 13 Jun 2023: Warning: 80% soon appeared to be totally wrong! See Note 401.
291. Richard Dawkins (2012) The descent of Edward Wilson, Prospect, May 24, 2012.
292. Maurizio Zanetti, Navin R. Mahadevan (2012) Immune Surveillance from Chromosomal Chaos? Science 28 September 2012
293. Tim R. Mercer et al (2009) Long non-coding RNAs: insights into functions, Nature Reviews Genetics 10, 155-159 (March 2009)
294. Vivien Marx (2012) 'Epigenetics: Reading the second genomic code', Nature 1 Nov 2012.
     "But DNA works with many partners, including 'epigenetic' factors, which influence gene expression in ways that don't involve changes to the underlying sequence" and: "... to control the activity of particular genes". Genes do not control gene expression? Who does the controlling? “This development has heightened awareness about the good technologies needed to study how the genetic code is put into action says Adam Petterson ! ... BET proteins belong to a class of epigenetic reader that targets histones, recruits multi-protein complexes to the spot where they attach and instructs cellular processes involved in reading genetic information ... So far, 96 histone methyltransferases have been identified in humans...”
295. The 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes, Nature 1 Nov 2012.
296. We now know that the haploid human genome has 3,080 (male) or 3,022 (female) million base pairs.
297. Nina V. Fedoroff (2012) Transposable Elements, Epigenetics, and Genome Evolution, Science 9 Nov 2012 (free access)
298. Dirk Schübeler (2012) Epigenetic Islands in a Genetic Ocean, Science 9 November 2012
299. Scott B. Vafai, Vamsi K. Mootha (2012) Mitochondrial disorders as windows into an ancient organelle, Nature 491, 374–383 (15 November 2012)
300. Charles Robert Darwin (1809–1882). Origin of Species. XIV. Mutual Affinities of Organic Beings: Morphology–Embryology–Rudimentary Organs.
301. See section genome sequencing and mapping in wikipedia. In 1995 the first eukaryotic genome, the budding yeast Saccharomyces cerevisiae, was completed.
302. Peter Langridge (2012) Genomics: Decoding our daily bread, Nature, 491, 678–680 (29 November 2012)
303. Warnecke T, Weber CC, Hurst LD. Why there is more to protein evolution than protein function: splicing, nucleosomes and dual-coding sequence, Biochem Soc Trans. 2009 Aug;37(Pt 4):756–61. (very useful, educational powerpoint presentation!).
304. Wenqing Fu et al (2012) Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants, Nature, Published online 28 November 2012
305. Panagiotis Papasaikas, Juan Valcárcel (2012) Splicing in 4D, science, 21 Dec 2012
306. Joshua B. Plotkin, Grzegorz Kudla (2011) 'Synonymous but not the same: the causes and consequences of codon bias', Nature Reviews Genetics 12, 32-42 (January 2011)
307. Dong-Dong Wu, David M. Irwin, Ya-Ping Zhang (2011) De Novo Origin of Human Protein-Coding Genes, PLoS Genetics 7(11)
308. David G. Knowles and Aoife McLysaght (2009) Recent de novo origin of human protein-coding genes, Genome Res. 2009. 19: "This is the first evidence for entirely novel human-specific protein-coding genes originating from ancestrally noncoding sequences. We estimate that 0.075% of human genes may have originated through this mechanism leading to a total expectation of 18 such cases in a genome of 24,000 protein-coding genes."
309. Dan Graur et al (2013) On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE, Genome Biology and Evolution , 20 Feb 2013.
310. The difference between prokaryotes and eukaryotes correlates well with effective population sizes, genome size and the ability of natural selection to remove "junk DNA". Large genomes belonging to species with small effective population sizes should contain considerable amounts of junk DNA. See: Note 309. So, Senapathy found "junk DNA" in eukaryotes and not in prokaryotes and concluded that eukaryotes looked more like random DNA than prokaryotic DNA. In fact the cause of the difference is population size.
311. Amy Maxmen (2013) RNA: The genome's rising stars, Nature 04 April 2013. 13 Jun 2023: Warning: "three-quarters of the human genome is transcribed into non-coding RNA" appeared to be totally wrong! See Note 401.
312. Gert Korthof (2012) New origin of life model fatally requires a nonrandom protein, 24 Dec 2012. (blogpost)
313. Is a variation on: "Surely You're Joking, Mr. Feynman!": Adventures of a Curious Character. (this has been the original title of the review...)
314. The human release factor eRF1 gene is 50.768 basepairs long and the protein is 437 Amino Acids long and has a specific, non-random, sequence. So, it cannot arise spontaneously. Mathematically speaking, every sequence can arise in a serie of trials long enough. But that is not the point. The abiotic synthesis of those specific DNA- or protein-sequences is the problem to solve.
315. Somatic Genome Mosaicism: But even within an individual, genomic variation exists. When individual cells of an organism have mutations this is called 'Genome Mosaicism'. For example: Somatic mosaicism can be caused by L1 transposition during embryogenesis. James R. Lupski (2013) 'Genome Mosaicism–One Human, Multiple Genomes', Science 26 July 2013.
316. Robert M. Brucker, Seth R. Bordenstein (2013) 'The Hologenomic Basis of Speciation: Gut Bacteria Cause Hybrid Lethality in the Genus Nasonia', Science 9 August 2013.
317. Kathleen L. McCann (2013) Mysterious Ribosomopathies Science 23 August 2013
318. Mitochondria Versus Nucleus, The Scientist, February 15, 2013
319. M. Paul Smith, David A. T. Harper (2013) Causes of the Cambrian Explosion, Science, 20 Sep 2013.
320. DNA Packaging: Nucleosomes and Chromatin, Nature Scitable.
321. "RNA polymerases are intricate molecular machines that transcribe DNA into RNA, combining RNA synthesis with the precise movement of a DNA template across their active site. Eukaryotic cells (those of animals, plants and fungi) have several RNA polymerases, each dedicated to the production of specific RNAs. RNA polymerase I (Pol I) synthesizes the ribosomal RNA component of the cell's protein-producing factories and so is crucial for cell survival, growth and proliferation; malfunction of Pol I can cause cell death or support the unrestrained proliferation characteristic of cancer cells". Nature 31 Oct 2013.
322. Kostas Kampourakis (Editor) (2013) The Philosophy of Biology: A Companion for Educators (History, Philosophy and Theory of the Life Sciences), Springer, Introduction, p. 3.
323. Tibor Gánti (2003) The Principles of Life, Oxford University Press, hardback. page 17. These are very beautiful insights from Gánti decades ago!
324. Robert J. Weatheritt, M. Madan Babu (2013) The Hidden Codes That Shape Protein Evolution, Science 13 Dec 13: "The authors determined that ~14% of the codons within 86.9% of human genes are occupied by transcription factors. Such regions, called "duons", therefore encode two types of information: one that is interpreted by the genetic code to make proteins and the other, by the transcription factor-binding regulatory code to influence gene expression. This requirement for transcription factors to bind within protein-coding regions of the genome has led to a considerable bias in codon usage and choice of amino acids, in a manner that is constrained by the binding motif of each transcription factor."
325. Tim Lenton, Andrew Watson (2011) Revolutions That Made the Earth, Oxford University Press. 448 pp. (Reissue edition: paperback 2013). (Chapter 4 and 4.6 Summary: the whole system view.)
326. Michele Clamp et al (2007) Distinguishing protein-coding and noncoding genes in the human genome PNAS December 4, 2007. A random GC-rich sequence (50% GC) of 2 kb has a ≈50% chance of harboring an ORF ≈400 bases long. See Supporting Information Figure 4 for the graph of ORF length statistics.
327. Kepa Ruiz-Mirazo and Alvaro Moreno (2006) 'On the Origins of Information and Its Relevance for Biological Complexity', Biological Theory 1(3) 2006, 227–229. However, single-stranded RNA could contain 'information' because it can fold. But, Senapathy is only concerned with DNA, not RNA.
328. Li Zhao (2014) Origin and Spread of de Novo Genes in Drosophila melanogaster Populations, Science 14 February 2014
329. Narayana Annaluru et al (2014) Total Synthesis of a Functional Designer Eukaryotic Chromosome, Science 4 April 2014: "Here, we report the synthesis of a functional 272,871 base pair designer eukaryotic chromosome, synIII, which is based on the 316,617 base pair native Saccharomyces cerevisiae chromosome III.". Other researchers have synthesized a bacterium's full genome, but the yeast job is orders of magnitude more complex. Furthermore, compare a yeast chromosome with human chromosome 21: 48 million nucleotides!
330. Elizabeth Pennisi (2014) Building the Ultimate Yeast Genome, Science 4 April 2014: To increase the genome's stability, they took out mobile DNA elements, such as retrotransposons, introns and other noncoding DNA. It took Codon Devices more than eleven months to deliver a 90,000-base circular chromosome.
331. Viruses are intracellular parasites and contain no ribosome, produce no energy and do not divide. See also: Pandoraviruses: Amoeba Viruses with Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes. Pandoraviruses contain more than 1000 protein-genes including 54 DNA-processing proteins and seven virus-encoded amino acid–transfer RNA (tRNA) ligases. The largest known viral genome Pandoravirus salinus contains 2541 protein-genes. The big number of genes does not make them alive; they still depend on living cells for reproduction.
332. Andrew G. Clark (2014) Genetics: The vital Y chromosome, Nature 508, 463-465 (24 April 2014): "Most noteworthy is their observation that the sex chromosomes of placental mammals, birds and monotremes had essentially independent origins, which means that patterns of gene loss and of specific retention of classes of genes on their Y (or W) chromosomes can be compared."
333. Compare with Daniel G. Gibson and J. Craig Venter (2014): "A biological cell is much like a computer – the genome can be thought of as the software that encodes the cell's instructions, and the cellular machinery as the hardware that interprets and runs the software." Nature 8 May 2014 (Synthetic biology: Construction of a yeast chromosome)
334. Jocelyn Kaiser (2014) The Hunt for Missing Genes, Science 16 May 2014. "the average person carries about 100 incapacitated genes–and in 20 of those cases, both the maternal and paternal copies of a gene are missing, creating a complete knockout."
335. Already at this point in the story the canonical genetic code is assumed. Or: rather some genetic code, because at that point in the origin of life any genetic code is possible. See: The elephant in the room. As an example: "reassignment of all three stop codons was found" in: Natalia N. Ivanova (2014) Stop codon reassignments in the wild, Science 23 May 2014. The effect of a stopcodon reassignment to an amino acid is a longer protein. A stop codon reassignment could be in the nuclear or mitochondrial DNA. [23 May 2014]
336. It is easy to forget that introns never get spliced out in the DNA, but only in the mRNA! Remark inserted 25 Jun 2014. Furthermore, catalytic RNAs play a dominant role in this processing, which represents a major involvement of ribozymes.
337. Wolf Reik & Gavin Kelsey (2014) Epigenetics: Cellular memory erased in human embryos, Nature 31 Jul 2014.
338. Mycoplasma: the codon UGA encodes the amino acid tryptophan instead of the usual stop codon. 31 Jul 2014
339. Matt Kaplan (2012) DNA has a 521-year half-life, Nature, 10 Oct 2012 1 Aug 2014
340. Bloom K, Joglekar A. (2010) 'Towards building a chromosome segregation machine', Nature, 2010 Jan 28
341. Suzanne Clancy DNA Transcription, Scitable, Nature Education.
342. However, if 'no other causal factor' than DNA is required to produce a human being, then 'the organism does –in a sense– compute itself from its genes'! So, what's the problem? He contradicts himself. For Senapathy the problem is quite different and serious: he has no cellular machinery for reading DNA. 9 Aug 2014
343. Genomes. 2nd edition. Chapter 7 Understanding a Genome Sequence. Stewart Scherer (2008) A short guide to the human genome states 16.995 to 21.461 nucleotides (bases). (p. 25)
344. Joanna L. Kelley, et al (2014) Compact genome of the Antarctic midge is likely an adaptation to an extreme environment, Nature Communications, 12 aug 2014. See Supplementary tables.
345. Addy Pross (2012) What is Life? : "All modern life forms depend critically on this interdependence. DNA, the nucleic acid in which all heritable information is coded, cannot replicate without the elaborate involvement of protein enzymes, and those proteins cannot be generated without the prior existence of the DNA molecule, which codes for those enzymes. ... The RNA-world hypothesis appears to resolve this dilemma... " Chapter 5. 26 Aug 2014.
346. Emily Singer (2014) Chemists Seek Possible Precursor to RNA, Quanta magazine, Feb 5 2014.
347. Thousands of never-before-seen human genome variations uncovered, Science Daily, 10 Nov 2014.
348. Guojie Zhang et al (2014) 'Comparative genomics reveals insights into avian genome evolution and adaptation', Science 12 December 2014
349. Hui Y. Xiong et al (2015) 'The human splicing code reveals new insights into the genetic determinants of disease ' and editorial: Roderic Guigo, Juan Valcarcel (2015) Prescribing splicing, Science 9 Jan 2015. "These [SNVs] include synonymous changes within protein-coding sequences, generally assumed to be functionally neutral, as well as missense or nonsense changes whose effects on protein expression may be more dramatic than anticipated because of their impact on the splicing process."
350. Ed Yong (2015) Microbiology: Here's looking at you, squid, Nature, 14 January 2015
351. Michael Weinreich (2015) Molecular biology: DNA replication reconstructed, Nature, News & Views, 26 March 2015. The core replication machinery has been conserved throughout evolution, from yeast to mammals.
352. Edward J. Grow et al (2015) Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells, Nature, 11 Jun 2015. "transcripts of HERVH, and of its regulatory element LTR7, were detected before EGA ". (Embryonic Genome Activation)
353. The cells' toolbox for DNA repair. Nobel Prize Org Press Release 7 October 2015. See also: Popular Information: DNA repair – providing chemical stability for life (pdf), and "Before his (Lindahl) work, "I don't think anybody really considered the idea that DNA requires active engagement by a set of housekeeping processes to keep it in a stable state," says Keith Caldecott" in Nature, 7 Oct 2015.
354. Robert J. Weatheritt, M. Madan Babu (2013) The Hidden Codes That Shape Protein Evolution, Science 13 December 2013
355. By the way, successful human fertilization requires an interaction between two unique proteins: Karsten Melcher (2016) When sperm meets egg, Nature 15 Jun 2016. Two proteins are: Izumo1, which is produced by sperm, and Juno, its receptor on eggs.
356. David S. Booth & Nicole King (2016) Evolution: Gene regulation in transition, Nature 23 Jun 2016
357. Fateful imprints, Science 13 Jan 2017
358. Suzan Mazur (2017) Eugene Koonin: The New Evolutionary Biology, Huffington Post, 02/03/2017. [my criticism: Koonin's genomes evolve in a vacuum, they do not live on a planet, and are not influenced by down-to-earth factors as physical, geochemical and climatological factors.]
359. Yasutaka Kakui, Frank Uhlmann (2017) Building chromosomes without bricks, Science 23 Jun 2017
360. Jeremy L. England (2013) Statistical physics of self-replication, The Journal of Chemical Physics, Volume 139, Issue 12 2013.
361. Tejas Dharmaraj, Katherine L. Wilson (2017) How chromosomes unite, Nature NEWS AND VIEWS 29 November 2017
362. Senapathy knows the existence of a Startcodon, he shows a Start codon in figure 10 on page 555 of the Genetics primer. A Start codon determines together with a Stop codon the Open Reading Frame (ORF). Calculation: on the basis of the frequency of stop codons, there are on average 3 ORFs of 21 codons in every sequence of random DNA of length 64 codons. Adding Start codons with frequency of 1 in 64, 1 of the 3 ORFs is truncated at position 10 on average. Taking together: 21 + 21 + 10 = 52 divided by 3 = 17 codons. So, the predicted average length of ORFs is 17 codons. This is smaller than predicted on the basis of Stop codons alone. 25 Feb 2018
363. According to Senapathy the left splice site is 9 bases long and the right one is 4 bases long (page 243). 1 Mar 2018
364. Circadian organization of the genome, Science 16 Mar 2018 ("The clock protein Rev-erbα regulates genome folding to establish circadian gene repression.")
365. However, according to Karo Michaelian (2017), photochemical pathways to nucleobases exist. (Thermodynamic Dissipation Theory of the Origin and Evolution of Life, p.124.).
366. "except bacteria and viruses, but including humans": please note that the genome of the MS2 bacteriophage virus is about as simple as a genome can get: 3600 bp. But according to Senapthy's theory the genome of this virus cannot, and a human genome of 3.2 billion bp can arise spontaneously. 28 Jun 2018
367. Bruce Alberts (2010) Model Organisms and Human Health, Science 24 Dec 2010.
368. K.J. Willis, J.C. McElwain (2002) The Evolution of Plants. , p.249. (8.3 Why no mass extinction in the plant fossil record?) 23 Nov 2018
369. It has been found that an ant-mimicking jumping spider that secretes a nutritious milk-like substance on which its young offspring are entirely dependent. The spider also continues to care for the spiderlings as they mature and become independent. Thus, this type of maternal care may be more widespread than has been assumed. Zhanqi Chen et al (2018) Prolonged milk provisioning in a jumping spider, Science 30 Nov 2018 30 Nov 2018
370. Procambarus clarkii (belongs to the Crustacea), the newly hatched stay attached to their mother. 26 Dec 2018
371. Samantha R. Edwards, Tracy L. Johnson (2019) 'Intron RNA sequences help yeast cells to survive starvation', Nature News and views, 16 Jan 2019: "Approximately 5% of protein-coding genes in yeast contain introns, and only nine contain more than one. By contrast, 90% of genes in mammals contain introns, with an average of eight introns per gene."
372. See also: 'Indian scientists protest against unscientific claims made at conference', Nature News 9 Jan 2019.
373. B. Kazemi (2011) Genomic Organization of Leishmania Species.
374. Matthew Cobb (2013) 1953: When Genes Became "Information", Cell, Volume 153, Issue 3, 25 April 2013, Pages 503-506.
375. Joshua B. Benoit, Mathias Kölliker, Geoffrey M. Attardo (2019) Putting invertebrate lactation in context, Science 8 Feb 2019.
376. Erich Bornberg-Bauer, Brennen Heames (2019) Becoming a de novo gene, Nature Ecology & Evolution 3, 524–525 (2019). 4 Jun 2019
377. Ken Garber (2019) Epigenetics comes to RNA. Science 5 Jul 2019. 5 Jul 2019
378. Human Genetics Revolution Tells Us That Men and Women Are Not the Same, Oct 24 2013. 22 Jul 2019
379. Linkedin profle Periannan Senapathy 1-1-2020
380. Michael Eisenstein (2020) How to build a genome, Nature, 24 February 2020. "At present, the only solution is to let living cells do the hard work of assembling fragments: Saccharomyces cerevisiae! ... that is not possible in the Senapathy scenario!
381. Lars Bode (2020) Understanding the mother-breastmilk-infant 'triad', Science, 6 Mar 2020.
382. Alan J. Warren (2020) DNA-repair enzyme turns to translation, Nature 26 Feb 2020
383. Jelke J. Fros (2021) An adaptive compromise - Conflicting evolutionary pressures on arthropod-borne Zika virus dinucleotide composition in mammalian hosts and mosquito vectors.
384. Paul Davies (1999) Life Force, New Scientist, pp 27-30. 18 September 1999. Please note Senapathy's book was published 1994. See also his "The FIfth Miracle" (1999) chapter 4.
385. Avihu H. Yona, Eric J. Alm, Jeff Gore (2018) Random sequences rapidly evolve into de novo promoters, Nature. Of course, as we know by now, this works only in a fully functioning genome in a fully functioning living organism. 5 Aug 2021
386. This is the email I received 6 Sep 2021 from Periannan Senapathy:
     • "Dear Gert,
       
       For business reasons, I had to search for my name on Google today. When I did, I observed that your website was the third to be displayed on the results page, and the caption under the website title stated the following, As you know, life in the animal kingdom is classified into the successive ranks of Phylum, Class, Order, Family, Genus, and Species. The core prediction of my theory is that fundamentally distinct organisms with unique body plans originated independently. By fundamentally distinct, I refer to the organisms that biologists had to separate into the highest-level taxa such as phylum and class. Humans are not classified in a high-level taxon, but the lowest rank of a species.
       
       For the reason outlined above, I would appreciate it if you could remove the statement "including humans" at the end of your description. It is a very prominent statement, which diminishes the core principle of my theory. What I had intended to stress in my book was that any fundamentally unique body plan, from the 'simplest' invertebrate to the most 'complex' vertebrate, must have originated independently. Nevertheless, organismal evolution would have worked on these body plans over millions of years, giving rise to numerous low-level taxa such as families, genera, and species, including humans. I hope this clarifies my view.
       
       Best regards,
       
       Sena".
       
       
     However, in his book there is no explicit statement that humans did not originate from the primordial pond. This review is about his 1994 book, and not about new interpretations decades later. Removing those two words would imply that around 8.7 million species of plants and animals have been created by evolution and are not independently born. This is in contradiction with the statement "Evolutionary Theories Are Fundamentally Incorrect" on the cover of his book and the first 4 chapters of his book. His 1994 theory would be changed beyond recognition. I will blog about this.
387. Senapathy's request to remove humans is a blogpost about Senapathy's request. 19 Sep 2021.
388. Are humans produced in Senapathy's Primordial Pond? Yes and No!, blog 27 sep 2021.
389. Chromosome centromeres are inherited epigenetically, Sciencedaily, Nov 9, 2011.
390. Tet methylcytosine dioxygenase 3 is an example of a protein that plays a role in DNA demethylation. Especially right after an egg and sperm have come together to form a zygote. 26 May 2022
391. "...in this case, find out what the smallest unit of the genome is necessary for a cell to know where it is in the body... how Hox genes help cells to learn and remember where they are. ... Different species have different structures and shapes, a lot of which depends on how Hox clusters get expressed.". Source: Scientists engineer synthetic DNA to study 'architect' genes, ScienceDaily, June 30, 2022
392. Rebecca Muir, Alan Diot, Joanna Poulton (2016) Mitochondrial content is central to nuclear gene expression: Profound implications for human health. Bioessays. 31 Aug 2022
393. Nick Lane (2022) 'Transformer: The Deep Chemistry of Life and Death', Chapter 6. "Mitochondria are now wholly integrated into their host cells, and their function is central to everything that cells do; not only energy, but also biosynthesis" (Chapter 6). The mitochondrion is much, much more important for the falsification of the theory of independent origin than I ever imagined. It was not apparent because references to mitochondrion and the mitochondrial genome are scattered all over this page.
     (b) "Even if the complete mammoth genome could be reconstituted successfully, letter by letter, it wouldn't work properly in elephant cells unless the mitochondrial genes were also replaced." (Chapter 6).
     (c) Quote from note 4 of chapter 6. 3 Sep 2022
394. Stuart Kauffman (1995) At Home In The Universe, page 38 bottom. 6 Sep 2022
395. Gert Korthof (2022) Did Nick Lane solve the origin of life? 5 Sep 2022. In this blog I point out that "Solving the origin of life is showing that non-enzymatic chemical reactions can create the basic chemicals of life. There can be no enzymes involved at that phase because enzymes are proteins. ... and they are coded by DNA." Ganti wrote already: "a living orgaism can never be developed from genetic material alone, i.e. only from chromosomes or the nucleus." (THE PRINCIPLES OF LIFE, 2003, hardback, OXFORD UNIVERSITY PRESS, p.126)
396. Charlie Wood (2020) Cosmic Rays May Explain Life's Bias for Right-Handed DNA, Quanta Magazine, June 29, 2020.
397. List of genetic disorders (wikipedia). 20 Nov 2022
398. Francis Crick (1988) What Mad Pursuit, Basic Books, p. 142. Jan 1, 2023
399. A Kondrashov (2017) Crumbling Genome, chapter 5.1 Fidelity of DNA replication. Jan 8, 2023
400. Futuyma, Kirkpatrick, Evolution, 5th ed, 2023 p.279. Figure 10.19. Feb 9, 2023
401. Laurence A. Moran (2023) 'What's in Your Genome? 90% of Your Genome Is Junk', University of Toronto Press, Release Date: May 16, 2023 chapter 5 (309/943) Jun 6, 2023
402. The reason for the update is that I discovered (1) part of it was based on wrong information of John S. Mattick and others, see: Note 401, and (2) Senapathy discussed 'Regulation of gene expression' in his 'Genetics Primer' on page559–563. (3) the paragraph likely contained information not avaible in 1994. This is the original text of the paragraph Regulatory sequences:
     

     ---

     "Genes are useless if they are not expressed and if the expression is not regulated. Even if one has found all 20,000 human genes in random DNA, that still would be useless.
     It has been found that introns account for at least 30% of the human genome and may be a significant, perhaps major, source of regulatory noncoding RNAs (116). An experiment concerning the relationship between introns and coded proteins provided evidence that some non-coding DNA is just as important as coding DNA. This experiment consisted of damaging a portion of noncoding DNA in a plant which resulted in a significant change in the leaf structure because structural proteins depended on information contained in introns (113).
     Genomes don't just encode proteins. They also give rise to various groups of noncoding RNAs that can regulate gene expression. Short RNAs that form from enhancer sequences might be one such class of regulatory RNA. The concomitant increase in non-coding content of the genome with organismal complexity supports the proposition that evolutionary innovations and expansion of regulatory RNAs were fundamental to the genetic programming of complex eukaryotes (293). As far as I know Senapathy ignored promotors (near to a gene's transcription start site), enhancers (far away) and transcription factor binding sites. Without regulatory sequences a DNA sequence is not a genome."

     ---

403. Denis A. Malyshev, et al (2014) A semi-synthetic organism with an expanded genetic alphabet, Nature, 7 May 2014. New base pair: pair formed between d5SICS and dNaM (d5SICS–dNaM).
404. Diana Kwon (2023) How scientists are hacking the genetic code to give proteins new powers, Nature.
405. How urea may have been the gateway to life, Sciencedaily, June 28, 2023.
406. PLOS ONE is an Open Access Peer-reviewed online journal. See paragraph 27 on this page: PLOS ONE article. Added: 30 Jun 2023
407. Wikipedia pages: Shapiro Senapathy algorithm (this page has several issues), Split gene theory (his book is mentioned), Life (his book is mentioned). Added: 30 Jun 2023
408. Senapathy writes: "When a very highly complex cell with a nucleus could be formed by a large genome containing an extremely large number of genes from the USP, it is quite probable to form an organelle [mitochondrion] with a far smaller set of genes directly from the primordial pond's genetic sequences. I am convinced that this is what had happened." Chapter 7 p.248. That's all! It's so simple! Added: 3 Jul 2023
409. Tomas Lindahl (1993) Instability and decay of the primary structure of DNA, Nature, 22 April 1993. Note: this is one year before Senapathy published his book. Added: 5 Jul 2023
410. A Kondrashov (2017) Crumbling Genome. Chapter 5 'Struggle for Fidelity'. (blog)
411. De novo genes are mentioned in Futuyma, Kirkpatrick (2023) Evolution fifth ed. page 267 with references. Added: 18 Jul 2023
412. Larry Moran (2023) 'What's in Your Genome? 90% of Your Genome Is Junk', Chapter 5 The big picture. This is a conservative estimate, other sources have much higher estimates. Added: 23 Jul 2023
413. Kara L. McKinley, Iain M. Cheeseman (2015) The molecular basis for centromere identity and function. Added: 3 Aug 2023
414. Geoffray Monteuuis et al (2019) The changing paradigm of intron retention: regulation, ramifications and recipes, Nucleic Acids Research. Added: 4 Aug 2023
415. In the Appendix Senapathy writes: "Genes constitute only a small proportion, typically less than five percent of the whole genome. These are only rough estimates. The rest is considered 'junk DNA', whose origin has been so far unclear." (Genetics Primer, page 543). Added: 11 Aug 2023
416. The concepts do not occur in Minkoff (1983). Minkoff uses 'epigenotype' in a quite different meaning. "Although many researchers proposed that DNA methylation might regulate gene expression, it was not until the 1980s that several studies demonstrated that DNA methylation was involved in gene regulation and cell differentiation" (Nature). Added: 11 Aug 2023.
417. As an afterthought Senapathy writes in note 117: "Remember, whenever we refer to immutable genome, we mean that the genome of one organism is not changeable to the genome of another organism with a new gene or a new body structure. The genes and the sequences in the genome can mutate, but the genome itself, speaking functionally, does not mutate." Added: 13 Aug 2023
418. Senapathy really thinks that biochemical machinery is present in the primordial pond to read DNA seqeunces: "These prebiotic chemical processes could also have led to the primitive but complex molecular machineries made up of prebiotically synthesized RNAs and proteins, not coded by DNA, capable of reading the messages contained in DNA sequences..." (page 206 chapter 6). Added: 16 Aug 2023
419. Amazingly, Senapathy is aware that he needs splicing sequences: "In our experiments in which we illustrated that we can find the genes of today's living animals and plants in random sequences, we have not included the splice junction sequences at the junctions of the exons and introns. We can certainly consider an experiment that includes the splice junction sequences. Although we have not done such an experiment, it is certain to yield similar results." (page 282 chapter 7). So, he knows things without doing the experiment! Added: 16 Aug 2023
420. "It is quite conceivable that the genomes of sexually reproducing multicellular organisms were also assembled as eukaryotic cells." (page 300 chapter 8) Added: 17 Aug 2023
421. Apparently, surprisingly, Senapathy knows: "In sexually-reproducing animals, development always begins with a single cell called the zygote. In most cases, the male (sperm) and female (egg) sex cells, called gametes, each containing a single (haploid) set of chromosomes, unite to produce the diploid zygote, which develops into the embryo that forms the offspring." (page 307, chapter 8) Added: 17 Aug 2023
422. But natural selection in this form means only to survive or not to survive. But this not enough. Survivors must reproduce otherwise they do not contribute to the next generation. That means in the majority of cases sexual reproduction. Added: 18 Aug 2023
423. On the Wikipedia page Split Gene Theory the name "Senapathy" occurs 47 times! This is extreme! Added: 22 Aug 2023
424. Senapathy rejects evolution: "Biologists have always been taught to believe that evolution takes a path from simple to complex systems. Because of the frame of mind and the world view about evolution and the fossil record, scientists were forced to take the simple → complex evolutionary route to explain how complex life evolved starting from the 'primitive' prokaryotes.' (page 517). Added: 23 Aug 2023
425. "but because of Darwin's subtly convoluted way of laying out his arguments and facts, filling gaps in knowledge by making extensive use of imaginary scenarios" is a quote from Richard G. Delisle, James Tierney (2022) Rereading Darwin's Origin of Species: The Hesitations of an Evolutionist, first chapter. In the same way as Darwin was not fully an evolutionist and incorporated many anti-evolutionary ideas into his work, Senapathy incorporated many evolutionary ideas into his anti-evolutionary theory. Added: 27 Aug 2023
426. He is not a biologist. Maybe his lack of a typical education in biology was, in part, what enabled him to arrive at his distinctive views on the subject. I think if he had had a more conventional education, if he'd come up through the ranks and had taken the standard biology courses and so on, maybe he would have done less interesting work. See: David L. Chandler (2023) Could the Universe be a giant quantum computer?, Nature 25 August 2023 (is about computer scientist and physicist Edward Fredkin). Added: 2 Sep 2023
427. Sleeping embryonic genomes are awoken by OBOX proteins, Nature 17 July 2023. Added: 2 Sep 2023
428. Tiny mineral inclusions picture the chemical exchange between Earth's mantle and atmosphere, Science Daily Aug 31, 2023. Added: 3 Sep 2023
429. If one searches for 'the origin of species', the results are found only in his discussion of Darwin and in the Notes. Not in his own theory! Revealingly, the title of his book is: 'Independent Birth of Organisms', not: 'Independent Birth of Species'! Added: 4 Sep 2023
430. Albert Eschenmoser (1925–2023), Science 14 Sep 2023. He investigated alternatives for DNA, and concluded that "hat the evolutionary choice of RNA and DNA was made from a diversity of constitutionally related alternatives on the basis of functional criteria.". Added: 15 Sep 2023
431. "He conveniently provided his Primordial pond with unlimited powers": Senapthy's primordial pond has no limits, it has unlimited power, it is all-powerful. There are no limiting environmental factors. This is not a good property for a theory. A good scientific theory describes limits. Natural selection is not all-powerful: it can be overpowered by random genetic drift, especially with small effective population sizes. Natural selection cannot produce perfect adaptations. Natural selection cannot eliminate (all) junk DNA. Added: 20 Sep 2023
432. The SRY gene: suppose the SRY gene would end up not in the Y-chromosome but in one of the 22 autosomes! Possibly, all individuals would be males. Because of the effect of SRY, there could be no females. End of a possible species. Added: 6 Nov 2023
433. Magdalena Zernicka-Goetz, Roger Highfield (2021) 'The Dance of Life: Symmetry, Cells and How We Become Human', WH Allen. Added: 12 Nov 2023
434. Silvia Monticelli, Petr Cejka (2024) DNA sensing and repair systems unexpectedly team up against cancer", Nature 10 Jan 2024. 18 Jan 2024
435. review of 'Gene Machine The Race to Decipher the Secrets of the Ribosome' on NHBS website.
436. Brendan R. Camellato et al (2024) Synthetic reversed sequences reveal default genomic states, Nature 6 March 2024. 11 Apr 2024
437. Kseniia Dudnyk et al (2024) Sequence basis of transcription initiation in the human genome, Science, 26 Apr 2024. Perspective: How DNA encodes the start of transcription. Transcription is much more complex than Senapthy imagined. "Furthermore, by comparing human and mouse data and sequence conservation across 241 mammalian species, we show that the transcription initiation rules are conserved across mammalian species." This points to common descent (of mammals) contrary to independent origin. 26 Apr 2024
438. Samuel C. Ginther et al (2024) Metabolic loads and the costs of metazoan reproduction, Science, 16 May 2024. 16 May 2024
439. Carissa Wong (2024) How much energy does it take to make a baby? Researchers are rethinking what they know. Nature, Open access. "...When you switch to live-bearing, there's a significant increase in the indirect costs — that's the cost of holding the baby inside you longer and moving around and carrying it,...". "A lack of women in the field might have led researchers to pay less attention to the indirect costs of reproduction, Marshall suggests."!!! 25 Oct 2024
     

Further Reading

• Periannan Senapathy's company Genome Technologies. Note: this seems to be no longer Senapathy's homepage, but of a commerical firm (noted on 16 Jun 2013). Here is a snapshot of his website genome.com taken in 2001 by the WayBackMachine. Please note the self-assured language Senapathy uses about himself and his achievements.
• Senapathy's new home site ("The page you requested was not found" on 16 Jun 2013).
• Senapathy's immodest autobiography. ("The page you requested was not found" on 16 Jun 2013).
• Independent Birth of Organisms - A New Theory That Distinct Organisms Arose Independenlty From the Primordial Pond Showing That Evolutionary Theories Are Fundamentally Incorrect (1994). Genome Press, Madison, 635 pages. The book is free available as an Adobe pdf file (3 MB!). Fast internet connection recommended. The pdf file is full-text searchable, which is extremely handy for research purposes (recommended for any book! Each book should also be published on CDROM!) [Today: ebooks]. Error: ("The page you requested was not found" on 16 Jun 2013). Luckily, I have saved the pdf on my PC.
• Here is a list of publications of Senapathy P (Periannan) from the BioInfoBank Library. More on p.598 of his book. Please note that peer-reviewed journals are included in the list, but as far as I can see from the abstracts those publications do not mention his theory of independent origin of organisms!
• PRWEB Genome Data Proves False the Theory of Evolution, New Theory Shows Complex Animals and Plants Originated from Prebiotic Chemistry, December 15, 2010
• A layman's summary of the new theory by Jeffrey Mattox. With many links (some dead links). Mattox is an electrical engineer who 'discovered' Senapathy. The page is no longer maintained.
• Double helix: 50 years of DNA (from Nature), containing a collection of overviews celebrating the historical, scientific and cultural impacts of the discovery of the double helix. All content is free.
• Gert Korthof: A Chemist's View of Life: Ultimate Reductionism & Dissent. A review of Schwabe's book.
• Gert Korthof: Independent Origin and the facts of life. Reasons from developmental biology, genetics and ecology (please note that I skipped reasons from evolution biology!).
• Gert Korthof: a review of The principles of Life by Tibor Gánti. (the origin of life)
• Gert Korthof: a review of Lynn Margulis and Dorion Sagan (2002) Acquiring Genomes. A theory of the origin of species. Recommended reading. If anything contradicts independent origin then it is Margulis' now well established symbiosis theory.
• Gert Korthof: The Feathered Onion is a review of Clive Trotman's book. Summary: Is the time span for the origin of life on earth too short?
• How Many New Genes Are There? Science Vol 311 24 March 2006 1709. This article uses computer generated random (intron-free) cDNA sequences of 2000 bases in length and concluded that by chance 1247 of 20,000 (6,2%) contain Open Reading Frames which could produce proteins of 119 or more amino acids.
• Robert M. Hazen, Patrick L. Griffin, James M. Carothers, and Jack W. Szostak (2007) 'Functional information and the emergence of biocomplexity', PNAS published online May 9, 2007. "Here we explore the functional information of randomly generated populations of Avida organisms." That is random genomes are generated! This would be a modest but careful way to explore genomespace and the probability of random generation of a funtional genome.
• Periannan Senapathy et al (2008) 'Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences', Plos One, October 20, 2008. Open Access. ("and that a machinery was required for removing the genetic waste.": the concept 'genetic waste' has only meaning if a functional genome exist. Similarly, 'stop codon' only has meaning if the genetic code is already established.) Please note that the book reviewed on this page is present in the PLOS article as note 36, but the subtitle 'A New Theory That Distinct Organisms Arose Independently From The Primordial Pond Showing That Evolutionary Theories Are Fundamentally Incorrect' is omitted.
• T. Ryan Gregory and Niles Eldredge (2008) Spore biology. Surprisingly, this page is usefull for Senapathy supporters, because Senapathy's theory is like Spore Biology (need to elaborate this).
• Periannan Senapathy (2013) 'Theory of the origin of complex eukaryotic genomes from pre-biotic random genetic sequences', 14 Mar 2013 - 12:00pm. Lecture in the Evolution Seminar Series (ESS) of the J.F. Crow Institute for the Study of Evolution, University of Wisconsin-Madison. (reported to me by Tyler Valkoun from University of Wisconsin-Madison).
• Gert Korthof (2021) Senapathy's request to remove humans is a blogpost about Senapathy's request. 19 Sep 2021.
• Gert Korthof (2021) Are humans produced in Senapathy's Primordial Pond? Yes and No! internal inconsistency in his theory, blog 27 Sep 2021.
• Gert Korthof (2022) Did Nick Lane solve the origin of life? blog 5 Sep 2022
• Gert Korthof (2023) Periannan Senapathy (1994) claimed that the human genome consists of more than 90% junk DNA, blog 04 July 2023.

Nederlands

• Gert Korthof (2011) Senapathy publiceert in Nature Precedings on korthof.blogspot.com 7 Jan 2011.